( T()I I N111 E

si sistcnltil colllplcx al collaunicatici intcrcclularc

C) 9 lili 1lltll tll II1l cStC t11l t()t tlilitar arillonios. alcatuit din dili_Nritc sistcnlc
lll1lcti()ncll _ c al c sc i111lticn/ca/a si sc contl oleaza rcciproc, printr un sistelll dc
c( nl lictltii ll tcl c l lLll c CXtrCIn dc colllplcx.in vedcrca n cntincrii in lil litc norlllalc a

II CI1 0KINI: rc8ru
crnlclltlI(lC :

iitt)1)F )tCHIC i

lactorrrl lccrozaut al
l tunl()ril()F.pr()dus in principal dc macro gele activate, dar si de r-ur-rhc alte
e clLric. cr.r Lrn spcctrlr larg cie actir,rni biologicc pc cclLrlclc tinta imune dar si pe
altclc din alhra sistcmurlr"ri irlLu-ritar)
iclrrrcnLrl rlc ,, itrtcrlcukir.tii >> clcriva clc la l'aptul ca accstc cjtokinc :;unt
rCSP()nsabil dc con tinicarca dintrc lin k2ci ,cCltliC aie sisternr-rlui in-runi1ar. ial tcrn-ienul
ilc ,, irltij]I991r.1_111e_r inc
-eL.:__].l L.:lpggiti[c3_4gg$gl_g{qkinc dc a intcrlera cr-r infectia
i irui:i rr Lrttci cciLilc.
t'iLoliinclc pot [i clarsillcaic si tinand cont clc surselc celularc : astlei, t1gtoh.11glg
sLrnt prorlusc c1c lintfircitclc l si l] (si nu numai). rnonokinelc sLtnt citokine secrctatc dc
nrc,nocite. s.it. nr.d.
ll nltl tll Cit()killcit)F CunOSctltc cstc l )artc nlarc(pcste 50 de spccii lllolectllarc)si
l lnlli tll l() crcstc in contillLlarC i lstibl sc cunosc pestc 20 de tipLlri dC interfthroni,pcste
18 in Il Hkinc an d pc c l i carc aoncaza asupra
1 91 9 yu aSupra
till 11 1-i
clupiu citoliinicn. clcvinc clin cc in ce nrai popr"rlara. r-narturic stand nunrcroasc[c
i
rric,.lir'lrnrcntc bitrloeicc pc bitza dc citol<inc. aflatc in uz sztr-r : cale dc autorizarc pcntru
! nt,'r)ri UCCt'fi1 pc illal.i

:NI 11ltl ICtlKINI]l 11

ict,t()1 li Ct)1lcxit:1111() 1lc tiro-1l l ino cndocl,inc

it.lli.rtrli rrrrrpirllcr srrrr biochclza aclivitrtcrr- crcstL'rcLr. urLrltiplicarea si lirnctiile oelulelor

irnLrnc. tlcci srnrt rclcvarati lN'ltlNOMOI)tJl.A'fOl{[ si au capac,itatca de a intertinu un
.r, lt' r lirl t i
. L iir, t t'c ee I tt c 1,ft rirffi
I rr I ttL I

 IntcrlcLrliinclc sLnrt pxrclusc clc limlocitele J'si Il. cle macrofage. dc celulelc
cndotclralc si cic rnultc altc tipiu'i dc cclr"rlc. I)c asetncnca. multe cclule ale organismului
pot clcveni tir-rla actir-urii interlctrkinelor: cciuie osoase. hepatclcitc. precursori medulari.
s.zr.r-n.d.
Utiliz-arca limlbkinelor in tcrapcutica depinde de disponibilitatea lor precum si de
clirrlitatcu si 1-rurilatca lor: rancianrcnlclc dc obtinerc plccanci clc Ia limlocitele uuraue. prin
telrnicj tr;rrlitionalc. srrrrt slabc. rlar prin inuincric tcnr-tici.r sc pot obtinc pe scara larga.
In Lrltrnrii uni- nlrrilc llnrc chinrico larrlaccuticc (Snrithhlinc lleccham. IIolfman
l.a I{ochc. s.a. )prcctLnr si cclc s1-rccializ.atc ir-r r-rtilizarea ingineriei genetice (Genentech.
Ilit,ucnc- ('ctrrs. s.a. ). sunt tbarte preocrqralc pcntrlr a lansa pe piata *int_grlerlkine
lccornbinatc.
- Irrtelcsul ;rentrlr accste substante este motivat de rnultiplele aplicatii tcrapeutice-
ciitrlI.cCiIl-Ccc2ltllais;lcctacltltlelszlparcatjin@a-tsfirnctiilor
sistcrntrlLri irnurrit:rr'. I)csi pzula in uromentul dc fhta cfrcacitatea terapetitl--ffi
-inLurlrrrl.incltrl in cr.tncct'tru r litst cottr lt()r dclll()11 ll l()r dc i11lt111()131()d
illu ti tlttt.lol ll it()ri

cstc l'rirrc I-rrutlatncntltt.

Sc cstinrcaza ca in crrlancl << 1-riata intcrlcr-rli.inclttr'>r \a ri valiza cLr cca a
antibirilicc lor.
Nomcnclatur:t
inolo8ie din cadrtl1 0MS a acordat
t11lit11lca 11ltcrn[tti()nalla a S()cictatii Pcntru lnl
irrtcllcrrl.inclor urr statLrt rlc i'rorrrcrrcl:ttr-rra ollciala si anumc pleser-rltalcali Il >,.,i1:;tr,'iittu
tlln lntlma(dc la L 18 pO ad J u
19_
it it(lc illtcil
1
lkinc I)cntll ilc antcrioarc introdllcerii
il acestei nonlcnclaturi oicialc
claLr clc
e rtlcrtt llcntrlr acciasi intcrlculiina.
i)rrircipiricIc e lrriictclistici alc irrtcllcul'inclrlr sur.tL :

- LrLi srclriatc rnolcculara mica (sLrb [10 l(D ) .

nrolccLrlclc sr-rnt glicozilate :
ptrt actiona autocrir-r. cuciocrin sar,r pitlacrin ;
irrtcractioncLL7,a cu receptori dc mare alinitatc existenli pe cliferite celule.
oirtc intcrlcrrliinclc lirrnrcaz.a o aclcvilriltul rctca biologica cL- transmitcrc a Lln()r
scrunirlc prin carc sc corrtrolcaza activitatca cclitlclrlr sistcnrLrlLri inrunitar clar si a altor'
ltllc c t c nti ll [lrtin accsttli sistcnl
int ukincl
ca dc Pilda in p SCI 1,111 119111,11 0 "1 1
llltcJctlkincl p()t actiona. 9 lq I
K C,S mull 1,9,1 ib
rCCir)1 ()C. lilandLl SC in rclatii spccilicc cu alti factori, culll ar li : intcrferonii, fhctor
`
clll lt()p()ictici dc cl cstcrc saLl altC bi()inoleculc i ctinoastcrea accstor interactiuni. va
p 1 1llite pc
riito
l illtclc8crCa nlai buna a nlodificarilol colllpOrtalllcntalc carc
lC()11ll lllia/ l stilrilc ini cti()asc si a lttccallisl cl()1,dc c()ntrol alc itinctii10r inlt!nitalic prin

F:t :1lStll

lt ll()1 3 inisnltll li la dil ritc tiplll i tlc stl es
1 1

St ldiatti_ in 'csti3ata stlb aspectul il plicatiilor ill patologia umana a st

lllicrlc ina 2( ll.-2)ic ista dcsttilc al 8 inlcntc cal c cvidCntia/a()pl ()dt:ctic al101 nlala dc
ll

h mH
91 uQi 1lnat sclcr()za 1-
tl il % Lim
scricc dc ll-2 cstc si tlll nlarkcr as()ciat dcclansarii rcactici dc rcspingcre in transplantclc

akrqcnicc (calc apartrnc acclcasi spccii. car cLr gcnotipuri dil-eritc). ln uncle cazuri at'
pLrteri li lirvoratrila l"rlocurca actiLrnii Il-.-? prin anticorpi ar-rti- ll--2.
\plicatiilc cclc rnai crtinsc aJc lt.-2;unt ins:i in tcrapia antitr-rmor-a1a. in special in
lLrirrrrri rr:rrrnogcrtc (curcirron't ta'',if-,r16ir,,r.,,,, ,.,-'t.1'g,..t 1 cLI obtincrca cle retlisiuni
srnirriilcltrrc
l.irurtarca cca rrilii sc\cra a Lrtilizarii lL-2 in practica. sc datoreaza ct'ectclor toxice,
-hipotensitine.
tlr.rtlLrsc prin tLrlbulari gilstro-intcstirralc (grcata. voma). r-nialgii. febra.
aliturii slib,'sLrltrar,'cntricularc. pana la tulburilri ncurologice (confirzii, crizc comitiale),
carrcl cslc ncccsiira sistzrrca aclr-ninistrat'ii. Rcclucerca rcactiilor aclt,crse sc va baza pc r.'iitor
pc asocicrca ll.-2 cir altc citol<iuc (cr. intcrlcrolri). sar-r cu citostaticrc. s.a.nr.cl,

Int FI LII ill[12

inlalla l ccolllbil141`l(r II -2)cstC()btilluta prill
intcrmediul unni proces de
rccorrrbliar . rcncticll carc irrrplica () sLlsa dc I:schcrichca (loli si cstc comercializ,ata srr[-)
i)( i nldcslctrlirn pt'rttlits
/ f t<0t l l.lKlN (C'c-tus. Arrtstcrdan.r)
/ ti. cLr Inrg pulberc liofilizata
de r-Lt--2
Irrdic'ltia aprolrata : tralartrcntul carcinonrului 9_glq[ei r-q-Lale in I'az.a cle metastazc
taT"r.lrcarcinomul rcnal nlctastazat al adutruluil. Mecanismul exact al actiunii
antincoplazicc nu este cLrnosctrt. clar se cunoaste r<llul ci in cresterea. diferentierea si
activlrrca rutrri anunrit tip cic celule (l-: NK/natLrrnl l<illcr) avancl un rol irnl-rortattt itt
pl'()cc-\ul .ic tlistt'rigcre a ccltrlclol tLrnlorutlc (;lroccs carc cstc rrrccliatt pc calc inrr.tna).
I)attrritrr rritci toricitati potcntialc (carc ar putcu pr-rne in pcricol viata). s-a
].!]C(rl]lil]l(.llItSlISciaiilciltlsiclCl.LirC.cLrlilartctliltltaateIltic.r@u.adica
lrrpolrLrl ilintrc cll'ctclc 1'lozitirc sr ec[c clc risc al tratiit'nctrtr"tlui cr: r\]ag!]gy\!t: pclltru ca
clcctcle ncclorite sr,rrrt legate cle doza administrata si dc fi"ecventa adn,inistrarilor (regimul
aprot-rat cic t:l)A pcutrll aclntinistrarca produsului cstc r-ru rcginr cu cloza lllat'c). sc itttpttt"ic
sLrplar cghcrcu cttr-rtir-iuLra pc toata clurati.l trzltanlcllturlui. dcoarccc cl'ccte lc indczirabilc nrr
pot li cltntinatc la nivclul administrarii clozclor active de rncdicament. Ijt'ectele ueclorite
sc p()t proclrrcc la nircl carclior,'ascr-rlar. rcnal. rcspirator si digcstil': pot aparc dcascntcnca
Llrclc nrirnilcstari sccr-rntlarc hcpaticc. hcnratoltrgicc si trcLtropsihicc. l:ttitt-tc liccr cnt ptlt
iiplrlcu l'chla" fiisoanclc" lrstcnitt. cclltlcc. rau gencra[. nrigrcne. rinite. reactii de
ir)t(Ilurlrirtil llr lrrctrl iIrict't.trii,--_r
[,nLri tltitja'--.:plfiii. l,ttr.q,Ltle ttiltal]lcrltlli! z\ldcslcukin.
--:=7
esre le plc/cntat .Lialrtul cu la uirii pacienti etu fbsl constatate rasput-tsuri semnif-rcative
tlLrpa un singr-rr tral-anrcnt. lirta clc agentii:rnLiqge-p.-La7.L9j-!1.4clit!o!el_i. la care un rasplrns
scnruillcati\ cstc e()nsttttat dltptt tttai ttrltllc scrii de tratanlg1l1.
iritcrlcr,rkrrrc'lc it.-1 ).1,_!1 sLu'rt inczr pr-rtin str-rdiatc. atat in ce privcste actiunea lor
hiolo!lie a. cat si-.- 1-xrsibilitatea obtincrii lor prin inginerie genetica. l)roducerca prin
irr!.irrclic gcnctica a Il.-i si ll -1. cstc in stLrc'liLr. llinci clonatc gcnclc carc codillea sitrtcza
ilccsl()l' i ntcrlcLil. i t-tc.
['tilizllilc e litricc llc ll.-l sLrnl : zrllcut laclitlprtitcct()t. clatorita clcctclor salc
stinrLrlcrrtc iisuprii hcnriitopoiczci- si- pcutru accclcrarca i indccarii ranilot'. lrincl ult
ntcclialor intportant al rlspnnsului orgatrisrlr-rlr-rr Ia inlcctii. inllarnatii st agrcsi'-rui.
Inclustria thruraccutica sc prc()crLlra ttrLtlt clc prcpararea l[,-1 in sperarnta cle utilizare cll
\ lL cr's ;"B-+lilt lr Il ctrl tt I clttrcct'Lr I tr i s i r-t lt t't roze i.
r.

o ( tt--: /stc r,,'r lactor clc cresterc hcmatopoietic,; adn-rinistrarea Il,-3 produce o
clcslcrc a nuuralulr-ri c1c critrocite. nc'utroTilc. eozinoflle. monocite si a placl-retelor.

5
I .*''l l.,ltl.'F.ltoNIl( II,'N )
mrdicamcnle biologicc cu actiunc imunumodulatoare

Intlc anii l9-lU-19(r(). ccrcctatorii

zru cicscopcrit ca anumite proteine eiiberate de
ccitrlc cancl itccstca sLlnt c\plrsL'agrcsiLrnilor unui virus. pcnnit celorlalte celule sa reziste
lir inlcctia i'irala: accstc cclr"rlc intcrl'cra cu replicarea r,'irala. dc uncle provinc numclc dc
intcrl'eron"
Descoperirea intert'eronilor in 1957, de catre cercelatorii englezi Aleck Isaacs si
.lcan l.inclcnnratr. a deschis calca unor inrportante si cercetari biochimice si medicale
.r:tti \r'il .i :lett r Ltl Lt i i rttet l c't titt ie.
lrritirrl. itrlellcrtrniiaLr {ost clcllrriti ca subslantc protcicc'. claboratc clc caLrc cclulc.
eiil.iI)ptll,is_lirrrtlcctiit.,',.r.iiig*.'..,rie'tatcac1ciitrta
rt!'e ---.---..-:-.--.-.-.'_--_-_--.':-------=-.=--.---._.:--,.,
IttLti r irul I'e1t.'e'trr .rlitr lir lrlte r irr,rsrrri. S-a cicscopet'it ca liccarc spccic prodr.rce rnai
nrLr-IIe'tilrirr'i cic intcrtcrorii.-fiicaE aiand [n spectru dc activitatc particular acelei specii :
nunrai intcrl'cxrnlrl unran cstc activ la on'r. -
<__ :
Intcrlclonii sttnt sccrctati in catrtitati loarte micr. clc Lrn nLu-nar mare cle celulc
lcLrcocitclc ;lrocluc jntcrt'crorl a. trbroblastii irrtcrl-eron*fi=lirnlbcitele interfcronllapt
pcr)tni rlrlc c\tnlgclca si 1-rLrrilrcarca lor a filst dilrcila nrult tirrrp: pentliL a stLrclia modill
ior ,lt: .tctir-rric si pcrttrLt a clcclua slLrclii clinicc. craLr ncccsalc cantitati rnali dc intct-Li:,roni.
\rccl ec nLi IlLltca li -irsigural clc intcrfcronii clitrcrati cLr cclr,rlc inl'ectate l'iral si obtinut-i
pr.irr rrrcludr tlasicc, rrtractilr'.
- SpcciiLr larg tle Lttiliz-rLlc a lliN- ltlr in clilcritc domcnii mcdicalc. a aLras clupa sinc
rrcccsitatca obtincrii lor in conclitii tot mai avantaioasc. Metoclele clasice de izolare si
pLrlilicarc s-alr tlovcclit incapabilc sa lirrnizczc cantitatilc clin ce in ce rnai mari de IFN
srriiciiatc clc tcstclc si tratanrcntclc clinicc. l'otoclata. prctlrl clc cost al ll:N-lor proclusi prin
ltccstc nrctoclc. s-u dovcclit un inrl-rccliuicr"tt lbartc marc in fblosirca lor iu vederea
rr()nrlrlll!'lii lr niirttrrtolrse boii Odatlr crr 1-lt'otir-rcclca prin, tclrnoklgia ADN: r'ccombin:rt s-
l lczolr ut irlzrl ploble nra cllnLitltii e aL si a costului
Nlctrldclc r.nodcritc r-ic ploclLrctic pr-- scara lalun. prin ingineric gcr-rclica- atr rcaiizat
izolirlca gcncior irrtcllL'r'onrlor- clonarca Iot'si 1-rr-orir-rccrca in nrasa prin tcrrlcniartic si
lirloscsc : - colibacili procccleul [3iogene ;
- clroidii - procc-clcul (icncntcch :
- r'icrnri clc nratasc pnrcccle ul l\4aecJa.
l)rinrclc stLrclii clinicc zrr-r ir-rccpr-rt in 1981.
l r irlcnticrca capacitatii lcucocitclor unrLurc clc a sintctiza Tl:'N prccr-rnt si a
pltrprictatil()r anlitLrllroralc alc LlccsLora. au in-rpr-rs rcconsidcrarea IFN-lor ca ult sistem
hiolor:ie ctlnttrlcr.
In conccptia acttritlit. lliN rcprczinta un grtrp de lrfornglecglle. care lac parte din
lirrrriiia nrrrc ll r;ubsiuntclr)r respousabilc dc cornunicarca intcrcelulara (nr:mitc cr_1OL<ttU) si
c:lrL'llLr rol in spccial in u;lar-ur-ca irntivirala. irr nroclil'icarca raspLrnsulLti ir-nr-rr-r. in c<tn1roIul
plol r lcnrri i si cli lL'rurtic.rii ccfirLliia. -----"

Structura chirnica a IF N
I)in pLrncl clc reclcrc structural. ll:N sunt ulicoproterne ce cull'ind ]46 *1_0.0_-*
ittuirtoitcizi si prczittlir s1-rccilicitatc de spc'cie : crista rrrai nlultc lont"tc dc IlrN c'lif'e ritc
p rTrlTili gL' rx lul c. rr'l rrsil nrll lcc rillLrri. grltl clc gl i cozi llrrc.

 i 0 I i l cinci tiP
i dc in H nil al ); (bC ); (3an :< u):
tl)( ()111()/()lll tll C()lltil rilCI pCntru II Si(2 iar cr()nlozollltll 1 2
tl ll
`2(()111
l]1
P
oni inai
Stint ctlnoscutc in l rc/cll1 0 diVcrsitate dc tipul i si subtipllri de ilntcr
alcs pclltrLl ll N ; cxpliCatia accstci divcrsitati ar putca ll lcgata de spccilicitatca
dilbritcl()r virtlstll i Carc au agrcsat ccitlla dc a lul18ul ilo8enici
l)csi scc 1 nta a11lin()aci/ilo dill dilbl itclc tiptiri dc llfN cstc diltrita.
l1lCi parti

l11l C01ll l1lC t lt tl ()r 11)

l()r allali ati si sc prcsupullc ca toclllal accstea ar reprezenta
)11(.l :lcil c al II ()
ll tcribr()nii pr illta anal()8ic structurala ilnun01o3ica cu intcrfcronii 6(o

11

FI T i lrt
lilnibkinc(dc tip intcrlcukillc)Intcrtt onii si sunt interferoni t`
likc''(asCmanatoril
p rcchci sinlilari) dar ctl sccvcnta protcica lllai liare

::i( 1lcI l inicl lcr()n:l()r intluclorii I N :ol .itcccplor ccluiclor tinta pcntru IFN
lcc tllisi 1 ll tiC prod lccrc a l N
In an carc cste secrctat in ctirsul stilnularii

lilll l citc l()r l l)1 in di `crsc substantc.1lu cstc inca clucidat.

() 111 l Ctl IFN al cI()cd lpll co1ltacttll cclulcloF Ctl indlictorii pcntru IF carc pot
ii lirali (Vir ls tll
aCizi llticlcici,
i polyribolluclcotidc sintcticc), sau l10n virali
([intrttchill()11 pil ilnlidill()1lC.Sa).
tlnii atit()1 i clasifica illductorii lFN-lor lni
i ncl lct()ri
11li crsali.acti vi astll ra llll10ritatii cclulclor(lcuCOCite,cclulc epitelialc.

libr()bltlsti).C 111l ar li tln lc bactcl ii.virtlstlri .acizi nuclcici sa

ill(luctt)li sp ciali.c trc acti()1lctt/a nunl ti astlpra anumit()r cclulc(CClulc NK
kill l si lilllit)cit ) si care s 11lt ccltllc inli_Nctatc c l vir lSuri cciulc
1lat lr ll

ll alntiscllc si 11lito8cllCI
t H11()

(l Ll ltO
ll tchllicilor nlodcrnc dc biol()8ic nlolcculara(cX:radiol arcarc l proteoliza
1

c11/i11latica sa). s a dCnlonstrat dupa 1980,cxistcnta rcccptorilor lllcl lbranari speciici

pcllll LI II N 1lind idcntillcate dotla tiptlri de reccptorl:
til
ll I_c( nl in ll. N (l si ll(o gliCOprotcina cu 4i100 KD,a carci sinteza cste sub
ticl cllclcllt[l lt)
PCnC dC pc cronlo/onlL11 2 1 1
- tipt:I II_sl)cciliC pcntl uI N a cartli Sintcza cstc dcpcndellta de cronlo/_ol 6 si
21
11l c 1/tll tris()nnici 21(sindl o1lou1 1)o vl1/ lon3olisnl)
s a detcctat pe lilllibcitc si

ll l ()) l c.()d 1lsitatc
11_ rin l 1(lit)1ln a rc tl lk tC lttarc dc rcccptori in col paratic cu
11

ccl ll lc(lipl()idcl accasta cxPliCa scnsibilitatca lllai lllarc a copiilor cti trisolllic 21 1a
ct IlfN I ris()11lia
( 2 1 cstc o pcl 1 lrbare gcnctica caractcrizata prin prezellta in
ccI llc a tlntli crollnozonl sLlpranulllerar,plasat alaturi dc perechca de cromozollli ol ologi
de acclasi tip l clinic.sc trad lcc prin nlalt)r natii diverse,adcsca connplexc,carc variaza
ltl1lctic dc srtlpa la carc apartinc crol l()z011lul suprantimerar.
I csattlLI I N rcccpt()r cstci ,pttCJ i CCCa cc limitca/a numarul de spccii
tltili/ lbil pcntl tl tc t ll ca aCtit111li H N- loF Sattlrabila datorita ntllllarullli lilllitat dc


 rr'ccptoi-i nrcn)branari. dc inalta alinit4tq ij pLqdggtl!a. pcntru ca gcncrea/.a Ltn senrnal
Liili ilr(luee sirrtezlr ;.rrrtrntittlt' pt'otcirtc.

/ cti lit lti biol()gicc cvidcntiatc 121 intcrfcroni

Actiunea antivirala a I N lor

il ll illtctizat dc()celula infcctata prilltl
un virus llu arc actiunc asupra cclulci
Ctll al ()d .ci lstlpra ccl llclor veci1le inca nci1lfcctatc.illstaland la nivelul acestora o
1 l

) tlllti 1 tll tt_ ccc l CC

1 1 ld lcc pl in inhibarca sintc/ci protcincl() virale, virustll
C tl

tl llltl
1 tl l ill llnposibilitatc l
i dc a sc lll lltiplica
/ cti ittttctl lnti ,il al lt cclLIICi illli_ ctate este lk)artc ptltcrnica rapida nespccillca
pc11li ti 111 i
.dtli stC
tl ln/itol ic si depcndcnta cic d( /a
Actiunca imun()I odulatoarc a I N-1()r
N c cl Cit l itctc i11lporta1ltc si col plcxc asupra
il lnui nulllar dc raspunsuri
111)tlnitarc
in
.i
`()
Si in vitl ()
ind ilnplicate i11lunitatca l11lnorala si imunitatea
t,itll 1 (l: d
:(linlinu[l
[t hipcrscnsibilittttii. dinlillu ca 1 fi_ nOnlc1lului dc rttcCtiC a
lll ()1_ l

ctilillc 1 lil til r()lil crtti t i a 1 21ntittlrllol 2till ll i Nl()r

Acti ca alltipl olili_ ativa sc cxclcita dcopotriva asLlpra Cclulclor tunloralc cat si
1l l

ll tll,
l CCI llcl() 1loFlllalc. acti inc calic cstc revcrsibila la illtrerupcrca tratalalentului si

tlcl illdc dc doza tiptll hist()logic al tunloriil tiplll de IFN: aceasta actillnc
t11ltil
l Cl Citata si asupra cellllel()r norlllalc cxplica l lielosupresia obscrvata in
()lilt rati

tci ll lliCtl.Prin actiL11lCa ast!pra lin lor hcnlatopolctlcc

( ctl 111 li l
ltcr1lica actitinc antiprolilbrativa apartinc IFN ullli intrc difcritclc
tip Hi ic illl FlOni istalld in sillcl
=iSlll dc actit11lc
int 1101lii acti()ll
1/ l nl[li alcs a lpra ttlllloril()l cLI CrCStcrc lcnta. cclulclc
i t111lt) [liC C 111(li llsibil t ilatcrit]1 ()1li Stillt accic lsi c l cclc nlai scnsibilc si la alti
titCllti Cit()lo lcI

itccol bin21rc l RcnctiCa in()l tincrca l N-1()r/tchnici dc obtincrc

1111)d losioc hattc pc pr()duccrca lFN lor in culturi dc cclulc(lctlC()Citc
li1111 citc. 1lbl ()blttsti).
:rlllata dc izolarc si purificarc s au dovcdit a n illeficcntc pcntru
obti1lcrca cantit ltil() clill cc in cc lllai nlal i solicitatc si la preturi dc cost l ult prca lllal 1.

liin l inl()ctlitc cLl nlCtodclc dc rcconlbillar _gcnctica_1__varianta produccrii lor pri11

tc1lll()l()8ia/ ))(rcco11lbinat l rczolvat pr()blcnla cantitatii(()btincrca pc scara industriala)
1
ct)st ll li tl prod ictic. S clLi COnturat 3 principale val iantc dc obtinere pc scara
ill(ltl triala:

() till l II ()F CLl

li bttctcl lil()F(1:SChCl ichca(loli)Ct1
lut() 8CnOnl nlodiflcat/
P occdctl1 131o8cnc al licat ill practica i1lca din 1 980 de catlic firllla internatiollala
13i() cll c tl obtincrc ll N^ lllli(l rcconlbinat. ctl actiullc idcntica omologlllui
1l tl

cndo8 1l si dc illalta p lritatc. carc poatc i folosit pentru prepararca f rlllelor

ilrnlttcctltiCc c()11)CrCiali/ lte lll N pl odtls dc bacteriile l] (loli arc o actiunc spccillca

Clll lnat() ll c ccllli l l ()( lS dc lcuc( citc. indtic llld ill cclulclc tlnlanc starca dc
/: 1 ll l[l l[l illi ctitl
ll l :
i

o ()btill FCtl l N I()rc lut()rul dF(ldiil()F(SaCCI ar()nl)cCS CCrcvisiac)/PrOCCdcul

(i !ic: lPlicat in prtlctica pcntru()btinerca IFN -1.l N -2 IIFN ;
C11

 (lbtinclca lirN-lor cu a-jutorul ricmrilor dc matasc. Procccleul Macda, pr-rs la punct in
.laponiii" clc catrc ccrcctatorul Macda ; se utilizcaza un AI)N recornbinat. care
lculizcuza inl'cctarcii r icrnrilor clc matase. r'icrnri carc procluc apcli cantitati mari clc
irrlcrlcloni si iu paralcl continua si sccrctia clc nratase. [)rin acest procedcu se proclucc
il:\ tL, ti;.tr'1-loirtc 1l ritilizat si lu prtieiLrccrca IlrN-lor p si y.

121ltltul illc(IiC lnlcntcI() cu interferon uman rccolllbinant

l: lst 111 :nlcl ()asc lllCdiCanlelltc carc contin difcritc tipuri si subtip Lri dC intcriblon
Ct)lllb lttllt

II N(1
( ()llcclltl [ltiilc si do/clc sLlnt CXpri11latc i1l LInitati: Llllitatilc dc illtcl fcroll sullt
( 1 rnni ntlt rin c()11lpararca acti 11lii
intivil ()ticc a lotullli lilbricat ctl actillnca

P rtl
li t:ltli intcr!lati()nal dc rcibrinta cc continc II'N ,obtintll dill lcllcOCitC ulnanc,
ltli ilit tl () l

1)c() trcc l Llllt pl otcillc. dili_ ritclc ibrn c alc i1ltcrii_onului allil nu trcbllic
ct)n clatc_st()CarCa trchuind sa lic ihcuta la tcnlpcraturi dc 2-8 (1.iar s()lutiilc illlectabile
lltt t btlic stt iic tloittltc
I)()/ llcccsal c dil itclol 1 indicatii alc produselor ctl intcrli_ rOn alila pot varia
lt tll 1 111 llti dc c : doza llcccsara tratalncnttil li i11 lc lcclllia c l tricolcticocitC eSte dc 3
111ili()[tl t11lit lti_c tt ldlllillistral c dc 3()1 i/sapta11lana,fata dc do a de 30 nlilioanc ullitati
tll)lict11 l ill Sarc()nlul K lP()si as()citlt c l SIIDA.dc 3-5 ori/saptamal a
lll c()P : Cttlaril tinci d() tri cxactc.pl ()d lstil carc arc()collCCntratic nlai lllal c
nti( htli s l lic Lltili/[111 n tl tI ldnlillistl arca do/ lol lllai 11lici

l aclil: t rJl p Ju_ 1lLttr:J 1111 alicl sunt dcpcntlclltc dc do/a Icvsibil la
illtr rtlPCrc1 lratt111lcnttlltti si p()t ii ltcnll ltc prin ttustal ca posol()8ici Rcactiilc scct11ldarC
it1 1li I F
11 1[11( :PrillCi tln si!ldl ()11l pscLld()8ri p[ll cu: 11 i on 1 bl tl.11 anspiratii.cclhicc
[1
tclli _ 11l i[ll li_[l tl ll li. 1 cactil di3csti .c ctli anOrc ic
8rcttlri.
'()nlal diarcc, dtlrcri
abd()11lin ll n ()dillcarca gusttllui,rcactii la nivcl SNC cu tulburari auditive,vcrt c,
d ) 11 ct)1 1/ic. 11
l ()/italtc. s()n 1101cnta.
ls()ara dilllintiarc a lunctiilor intelccttlale,
tal i dc tip hal lcillosc1l Si nlai rar crizc cpilcptilt)lIIlc, ial 121 11ivclul sistcllltll li
111 tll l l

nc ()
Pcrilill ic i pal cstc/il. nctlr()P ltil ti^cnltlratt:ri lil ctcic c 1litli() lsc llal c stlnt i

in/itolii_cdc11lc_ itlll h.tahical .palpit lrcli tol lcicc i

l

il _ ltl 11lI)()1 11 itH tF tli ttii
tl d

ltl lli ltll piclli tll [t i pr it. al( pccic lscaciLlnCtl Piclii si a nl ic()aSClor_ c accrbal ca
l

h ll) tlltli ltibitll. iar la lli 1 1 cllal. silldl ()111 1lCI ( tic_crcstcri alc LlriCClllici protcintlric i
,cl tll
11 i ltltol(, ic i lctict)pcllic 11 t)nll)()l) niC i la ni landcl() cnd()cl 11lc arc l()c
11 ()tlilict11 Ca C() ti/()lcn ici(cOnibl nl croll()1larnlacocincticii sc l ccolllanda ca 11.N stl sc
aclllllllistliczc intrc ()1 clc 20-24)_ hipOtiroidic dil inuarca elibcrarii estrogenilor si
l
1 01CStCr()1lllltli cil ctllant i cibcte secundarc nlctabolicc i crcsterea trigliccridelor
( 1 (lt( / 1) CrCStCrca crc tl Hncl l tircc: san3 lillc. iar la nivcl hcpatic. crcstcrca
tr[11
ttlllillti/clt)r si tl lk)slllta/cl()1 alcalill
lc()11
_
t 11llt_(lc tt 11lCnc 1. IDl ()d lCCl ca dc lntic()1 IDi alntiintcr10ron
11ltc/tl ciC illt 10 ()1l plill lchllic 1 / 1) rcconlbillat rcprczillta ull s lccCS al
indtl trici lll 11 clCCtitiCC Spcctl ll dc albcti ini iln care intcribl ollii allh aduc tin bcncnciu
t l tll) tlliC C tc l 1lltilCtibil c ctl cc tl dttS l l catltalca dc 11()i cai dc crcstcrc a clicacitatii
tlSt litt l13 spccial prin lllodilicarca rcgilllul li dc adlllillistrarc sau prin conlbinarca ctl
.ir[lli :

lti 18 1lti allti lsa a apal llt pcgintcrfcron ul,obti11 :t prill atasarca la nlolcctila d

Il]N c, 2ll rur.]an rcconrbinzrt a Llnui lant clc polictilenglicol (PllG). cLr o grcLrtatc
nrolcculura rlcclic clc 12.000 dc claltoni(D). cr-r aceleasi ploprietati- profil de siguranta.
lcuclii iidrcrsc- si curc sprc clcosctrirc clc ll:N cL 2l]. arc un clcarancc rcnal semnificativ
\cr/ur. rrstlcl cu tinrpul pllsrnatic clc iniurlatalirc (tl4). crcstc dc la 4orc la 40 cle ore" ceca
.r'l:r,'i ptr:iirilli u.inrirri:ti.lu.cll I'}l:(l-llr\ tl lll. I clata."saptanrana. crescatrd benellciilc
,;l irriec lrli liccslLrn.
1'ql!iq it1'tq1lp'tUtrtdLLhqlljJqegf1tlf_.fdlf:Sc scmnaiizalc lzr dozclc lblosite in mod uzual.
sLrnt sinrl-rtr)urc.lscnrani-lt()alc gripci. ca si la interf'eronui alfa. si in 85(% din cazuri reaclii
la locLrl inicctarii ( ciurcrc. inllamatic. nccroza) ph"rs moclificari ale starii mentale carc
inc I Lrcl clcplcsic- con litzic. anxiel.atc.

llcaetiilc urllcrsc pcnlru inlc'rfc'rour-rl gqllM. 1ac lclcrirc la un sindron-] ascmanator gripci.
lir nrajoritalca pacicntilrlr- a carui p.rzrvitatc cstc pr()portional clr cloza (tratabil clr
analsczicc si antitermicc)- icLrcol.rcnic. trombocitopenie. hipotcnsiunc.
Ii'atanrcntril e rr intcrlcron grinra nu rlr.rcc llt clczvoltarca anticorpilor ncr"rtralizanti.

l.ocurilc optiurc dc acL-nir"ristrarc a injectiilor s.c. cLr intert'eroni suurt deltoizii si

po11 i unca antcrioanr :t coitl-rsclor.
Sr-rnt in stucliu r-roi lclrnrc cle adrninistrare a intcrl'cror-rilor (tbrn-re cu administrare
plcltrngita : cu lil"rozorrti. cLr rratrici dc polimeri bioclegradabili, s.a.(
l)ireetiiie rrlrrrirlite in prezent i-lu ci.r scrlp stabililCa Lulor.inciicatii tcrapcuticc Lrtilc
irrtr'-o scric clc nralaclii consiclcratc it-i prczcnt incLrrabilc.

I ntrrii'ron tr-2:t
InrLrr.rorrrocllrlutor cu t',':,-lc J-B orc. clrrpa adminislrarc pcrlirzabila. i.v: adrninistrat s.c.
sirrr i nr.. picLrl scric c-stc la 4 orc.
iri.lie.rt in.
- hcpatita cronic:r [] la aciLrlti cu markcri c1e replicare virala,
- hcpatita clorrica C la adulti cr-r VllC pozitivi ,
- canccr clc rinichi. sladii al'ansale .
- lctrccrlic nricloicla croniczt :
- lr nr lirttt c r-rtanltt :
' lcrrccnric ctr tr-icolcr-tcocitc :
S Il ),\ si Slrrcorlr Kaposi r.rcsin'rlttorrraLie
I)r'o.lris . I{()lrl:l{()N -,\(l{ochc).
Iirll-,clc ini rlc dilcritc conccntnttii (l " -1.5 : (r . : ll : ltl \4.lr.T /tttl
()
I nte rl'e ron tr-Zb
Irrrrnor.r.roclulator. antiinl'ectios. anticzurceros. cll aceleasi indicatii ca si Interf-eron a-2a .

[)roclus: IN ll{ON-A (Schcring [)loLrgh" I]elgia)

Sol.ini. dc cli lcritc cot-tccntratii
Inierl'cron fl-!rr
ir)ri iriit irr ilirlitnrcntuI arrbLriirtoritr in scicrrrza nrrrltiplit. err rccitdcri. cr-r ccl putitr cloua
iillerrri ,.ic ri islirnclic ncrrrolttsicu Ilc o pcrioacla dc trci ani cor.tsccutivc: incctincstc
Irrourcsia iiir aiiclitiriit si scaclc ticcvctrta rccadcrilor.
l'roriLrsc:,\\/()N l;X ((icncsis l'hartla. (irecia. sol. inj. 6 .U.1.
Itl : lll I: ( Scrano. Anglia). pr-ribcreninj. De difcritc concentratii

Interleron fi-l b
IrlLrnorcglator'" lrntiviral. inclicert in sclcroza in placi. la bolnavi carc sc deplaseaz-a singLrri
si alancl r:cl prrtin cloiia aleicuri cu atingcre ncurologica in r-rltimii cloi ani. urmate de
rcntisi irni totaic sittr partialc.
l)rotiLis : lll:lr,\lrl:l{ON (Schcring. (icrnrania). pLrlb, pt.sol.inj. tl nril. tJ.i.
In ttllcron r\l-1.,\('ON- [
Irrclicat in hcpatita crorricei la bolnavi peste l8 ani. cu markeri serici de virus C, f'ara
Ircll\itl'c hcIltticlt,
\lur'( )ll)
l)roclus. l N'l'l:tt(; l:N ( Yanranotrchi [:uropc. Olancla). sol. in-i.
l)cgintcrlel"on rr-2a
Irr.lieut in lrcpritita cronica tip (-" crlnllrurata histologic. la pacicnti adulti si pacienti cu
c i r-r,za ()()nrpcnsalc.
i)r-otlris :l)L(i,\SYS (I{ochc. Anglia). sol.ini.
l'rginlcrlcron tr-2h
ln nr()r]()tclu1'ric" pcntrLr boluiirii aciLrlti cir hcpatitzr (l confirnrata. cLl markcri serici pcntru
lepl iearca r it'r-isrrIui.
l)r'otlrrs : I'l:(ilN I ItON (Schcrirrg PloLrgh I:r,rrope. 13clgia). pulb.lio[.pt.sol.inj.

R I :( () `!: INAltEA(11]Nl{ TI(lA IN 013 IN11ltEA llNOIt lI]1)I(:A IENTE
I

( 1()R11)lt(]itiiSTERl(:Al(lEl ll l 111 OIt SANCtJINE

('rcslcrca llz.ica a organisr-t'rulr-ri cstc rcglata dc htlrr"r"roni ciasici ca solnatoLropirra

hil"rolizanr holnronii tiroiclicni. cortictistcroizi si altii. In alura controlului global al
.r'cstcri i organisrrruItri. la nii'cl cclulzrr uetioncaz-u nunicrosi factori . c:arrc rcglcaz.a divcrsc
nrourcntc din ,.'iata cclLrlclor (plolilL'rarca. dczvoltzrrca. clilcrcuticrca). accsti factori au
ltisr tictrLrrrriti liictot'r dc crcstcrcl(i1: ((;l{()w l'll lrn (-tOlt). Iactorii cle crcstcre actioncaza
prin rlccanisn'rclc e.cncralc alc honnonilor clasici si sunt rcclrnoscr"rti dc rcccptorii
nrcrrrblitrrirri .

('iiLrlclc surrel,rinc srrnt r, italc iatlr oruarrisntulLti Llnriur: clc transporta

1'rcnlrrr r
orirlcnrrl. hrurna orgtrnisrnulLrr. asigurii imunitatca gazclei. au rol in coagularea sangelui.
ctu .

(ciLi lr;le sltngLrinc .lcr in lirnctior-ralc ;lrintr-un proccs lbartc corlpicx. care sc
,ir'si.iroirtr in rn.ri rrLrltr ctul-lc. irt carc cclLrlclc inraturc. pl'ccLlrs()arc clc ia nir.'cllrl maduvci
ii\()irsc sc nlilLiri,/citzil. irr r.ll()d obisl)Lrit accst proccs rcglator inl<lcr"ricste celulcle picrclute
in trnrpul actitrniior liziologrce zilnicc. Pe aceasta cale s<: produc milioane de celule
capirt",ilc sa lLrptc impotrira infcctiilor saLl sa inlocuiasca pierderile datoratc hcm<lragiilor.
\ii'litlt clil-xrcilatc clc a firrnra cclirlc sanguir-rc cu xrluri llziolouicc vitale se nunreste
I:i:ir:rlrrIoicrrr.
('lriril in irrirrrclc rlcccnii alc scco[ulLri XX. oat-t-tcnii dc strinta au dcscopcrit
p:.r,r,,t.r)lii iur()r'luetrrri circLrlanti carc rcglcrlza hcnratopoiczit- rlir-r pilcatc;rroercsclc
rrltclioarc au iost an.uuratc apr()apc o.j umatate cle secol. pana cand au fost descopcrite
srslcr-ire lc tlc culturi cclularc pc carc sc pLrtcalr dczvolta colonii cclularc "'in vitro".
('r'cstclcu si sLrpravictr-rirczi cclulclor sanguinc tirnpurii. cclule stcm. ncecsitaiL
prczclrtu unor lirctori :ipccillci. lIpt ce a cielcruinat iblosirca termenLllr-ri dc ]actql
strn)rilaLol ai colouici (('SI; coloru'stimLrlilting l'actor. tcnrcn cc provine cle la tchnica
.le uLrltrrurc la tliliitii nruri. a cclr-riclol proucnitoarc. ce^lglg's_tlnr. in placi c'le cultur:a).
incirblrt'-: in prczr.rntr-r luctrlr-ilor dc crcstcrc" cclulclc stcnr dau r-)zlst.crc unor ctlltlnii. mici
.rillonrctu'r ,,ic cciuic in elrt'irtecpc un proccss dc clif'crcnticrc splc Llnzl sau rlai rlultc lrnii
irr-:iruriosrrrt: I iltcliol a lirst prctcrat tcnricnul clc licpl!4!]illepgigliql dS CfeSl_Sfg
\lctoclclc clc pLrrilicar-c a Iuctorilor lrcnratopoictici au progrcsat lcr-rt intlc anii
1970- 1980: pe rlc alta partc. s-a constatat ca sangele continc cantitati extrcm de mici de
iiruturi Ire rrilrt.rnrrictici. i:rr crisicrtl.r.r irr s;.tnge a trriti rrtrrlttlr' [Ictrlri Ircrttatttl"ltrictici a
iitglcLrnlit ccrcctarca plir ind activilatca spccilica a ljccarLri lactor in partc.
irrtrtrrltrccrt:u tchnologici Al)N rcconrbinant a clcclansat o seric clc str-rdii cafe all
ri,-irrs o e ..qrlozic titr irtlirrnratii- inccl-ritncl ctr l9()0. llirrcl pr-rsi itr cvtclcutit si chiar izolati.
rrr.ii rrrr-i ir.ii: )() tic lactori ircrrratol-loicticr clc crcstcrc sr rrr-rr"rrarul lor cstc in r:olrtinua
L iC:iCl'e .

lrircltrrii hcnratol"rorctici rcglcLr/.Lt Lrlal hcnratoiroic /.a caL sr acti vitatca lirnctionala a
iclirlcltrI sliur,-rrirrc ntlrlure : 1-lrin lrctir itatc ltrr-rctionala sc ir-itelcg.c:
e ;'rr-olilcrarcu cclLrlclor (rcprocluccrca Linor ccltrlc sinrilarc):
. dile'r'cnticrca cclLrlclor (spccializarea saLr clobandirca Lrnor liurctii dilirite
tie cclc alc cclLrlclr)r stcur- prinritivc):
3 n-iiriur-rri'clr cclLrlclor' (schinrbari irr clczvollarc cc concluc Ia cclLrle sangtrinc
Irctive ii in prrnct cic r cclcrc liructionitl).

/
 lir pir-rs. iirctorii hcrlutopoictici nrobilizcaza cclulclc llicc sa sc dcplaseze dc la
r.rr i'lrrl nlrdrrr ci spinltrii in sitn!.clc pcriltric.
I:rista opt rnari tipLrri dc cclirlc sangr-rinc rnaturc- toate derirrate clintr-o popuiatic
Lrnica dc cclr-rlc stcur primitivc. clin maduva spinarii. (-'alca rnieloicla conduce Ia obtinerca
clotrrilclol rosii (cril,rocitc). a plachctelor sanguir-rc (tronrbocitc). a monocitekrr si a
rriliulrrlirgcl()1. llrccLllr si Lr glanr-rlt)citclor' (LrcLrtrtllilc. eozinolllc. bazolilc): calca limlbida
eontlircc la obtincr-cii clilcritclor tipurri clc liillocitc (linrfbcitc Il.'t')
l)enumirca llecarrri lirctor hcmatopoietic c{e crestcre. cleriva dc la celula tinta
It'crlrln't i r[ttltit- llsit sLll-]t
:

- (i- ('SI. lhctor stinrulator al colonici clc grani-rlocitc.

igttrtulocl lc - ctrlottr stitlul;ltirtg lirctor)
N4 ('Sl: thctor stiurulartor al coloniei cle macrol'age;
(nracrophau,e colonv slimulating factor)
- ( i\4- ('Sl; lactor- stinrulator iil coltlnici clc nracro{tigo granulocitare:
iir rrlrinr irc.st()r'lrci iirettrli. rnui erista sr alti lacturi hcnratrlpoictici clar carc uu sitttt
tictlrriti ea si cci clin lanrilia ('Sli (lirctori dc stinrr,rlarc zri color-riilor).
ll'}O lirctorLrl carc stinrLrlcaza prolilcrarca plachctclor- serngr"rinc(tron-rbopoictina).
I l'(,r llicttlriil curc olicntcazu diIcrcnticrca cclLrlclor stcrr sprc lini:r critroicla
( criiro po ictina ):

- Intcrlcirkina i (ll.-i) lzrctur slirnuizrtor ncdil'ercntiat al celr,rlelor susa din care iau
l-rristere o rrarietatc cle ctllonii nrirLr-:
- [ntcllcLr]iina 7 (ll.-7) f actor stintLrlator al prolil.:rarii si dilcrentierii linici linttoiclet
\.ii.

I;actolii hcnr:rtoltoictici surr-rt glicoprolcine. si sc cleoscbesc intrc ci pt'iu secventa de

:ririnorrt:izi si prirr nrtrclalitatilc dc glicozilzrrc (tiprrl clc lcgatLrra clin;lartca glucicliell.
lactolii hcnratopttictici clc crcsterc cncloguri se tbrntcaza prin cascacla
Ircnrulolloictica. clirr ccitrla stcnl. si sunl clcpozitati- citntonati in chleritc cclulc. tesuluri. cie
Lnrr-lc 1-rot ll clibcrati ir.r urma Luror clilcritc stinrLrlari 1cx: clc uittura inllarT"iatoric. tt-ttriori,
Jl,.- j

l)r'lrccsut rte protluctic. l:iccarc lirctor hcrnato;loictic cslc coclillcat clc o gcna ltttica.
errrr,ilriiitc il ol--rintrrl tlin tlilcritc si-rrsc saLr Iinri c1c cclr"rlc si cxprirnata in dilcritc sistente
l-.ioi,irlire ibrrr'trrrii sirtr rlrojdii). pcntrrt a procir.rcc l4ctori hcr.nrttol.rtrietiq pLi n 1'cqort]l]ptlls
gcuctica: gcnclc ofcl-r nratriLri 1-rcntrr-r procluccrca. obtitrcrca cantitatilor n-rari dc lhctor
llcntilt()p()ictic. f ili n i ntcnrctii irl tchnolosici ADN recontbi nzrnt.
Sr-rrsa obisr-rLrita pcrrtnr obtiucrea gcnci estc o linic clc ccIr-rlc tumoralc ( tr:n"ror ccll
linc)..ilrtoritrr rantliinrcntLrlLri sarr. l)u1'r:r cltlrarc. qcnu cstc cxprimata clc obicci in bacterii
(l ('oli). cclrrlc tlirr orsarrisnrul rnanrilcrclor (ovarrLrl dc cobai). sau cellulc de drojciie
(5ue e itaronrie cs ('cre r isi:rc). pLrtanciLr-sc producc cantitati Inari de glicoprotcina (lactor de
c|cslci'r). p|occsr-rl cic prrtrlr-rctic ncccsitancl tlai nlLtltc titzc.
(i\l ( Sl . a lirsr 1-rri nrrrl lirctor hcn'ratopoictic cic crcstcrc Lrman obtinr-rt prin tchnica
.\i)N lrcrtrtrbir.urnt (r(il\4 ('Slr): tactorii hcmatopoictici rcconrbiuati sc llsclllnr-llll e r-t cci
cnrlirgcni. crr crccptia unor mici r-nodificari ale secventei de aminoacirj. a gradului cle
r:liror:iilrrc. slrrr a irrnbcltlr. accstc aspcctc llincl cictcrnrinalc dc nrctttcla cle obtittere.
l'ot prin tchnologia.A[)N rccomdinat au lbst obtinuti si alti thctori: (i-CSI (rG-CSIr).
\1-i Si lrlr'l ( Sl:). il I (r'li.-l). s.a.

 l)rotl usc l'a rlr"l:rceu ticc cu l:rctrl ri hcmatopoictici rccom binati

r'{,i - {'Sl''
l''ll.(; \S'l ltllt (lX'ly l)r'orlrrsc: Nl:t i)(X;l'N (llochc. ('unatla: Arrgcn- I:uropa. Stln )
Sol.inj. 300rncg/rnl: .180 ntcg/rll
(;I{ANl..lI-OKtN (I)ompc-lrstcvc-l)cnsa. ltalia. Spania)
(lltAN (Kirin Sank1,o. Japonia. 'fairvarr. China)
- lliclrir unran clc stitnr-rlarc a c<lloniilrlr clc granulocr,'tc. ohlinut prin tel"rnologia
,\l)\ rccon']burant. ctil'c stimrricaza prolilcrarca si clil'crcnticrca ner-rtroflleIttr.
brrzo l r lclor- rnlrstrlc i tcltrr:
- csic rndicrrt in lratanrcntul prolilactic si.rlt curati\,al llcutropcl-lici asociata
chinriotcrupicr antitLrtrtlralc sau treursplantulLri cic nraclrrvzr ()soasa" Lrncoli ca
lurl.jLn'anl in tratarncntul infcctici virale:
- ncLrtrolilclc procir-rsc crl raspuus la trailamcrrlul cu Nculrogcn. aLl lirnctii norrlalc
suLr uctivalc: clupit o;lrirca tt'atanrcntului cu Neupogcn. nur-narul ncutrofilclor
poliuiorlbnuclcaue circr.rlantc scade cr-r -50%r. in prima si a dolra zi. ca apoi sa se
norrnalizczc intr-Lur intcn,al cic l-7 zile:
sc rrtlrlirrislrcitzu s.c. sau i.r. solLrtia apoasa injcctabila- cloz.a rccor-r-ranclata fiincl clc
)itll: i'.,' r ()l'lr /i.
pr iriui rrrlectie cLl \cLrpoucrr trc[ruic clcctLlLlllr tlr-rpa l-l ir clc la tenlriui-rlr:a
e hirniotcrapici citotoricc: ilrrrata tratanrcntullri poatc r-ncrsc pana la l4 t.ile- tn

iirne tie rlc rloza si schcnia dc chinritrtct'r.tpic citrrtorie a Lrtilizata:

- r'cactii achcrsc: clureri urusculiue si ()soasc. Llsr)arc pana la moclcrate (l0%r) si
sc\crc (i9,). rlrrrcri stirpanite ;lrin aclrninistlarcu clc anti:rlgicc: cl isLu'ir ustlarc si
nrildcrirtc. an()l'c\ic. clcata. \()llit. cliarec. astenic. alopccic- r'initc- tr-tse . plr-rt'it.
JLrrcli toracicc. clLrlcri clc gat. constipatic. ctc. la dozclc uzualc recomandatc, pot
silr'\cni si rrrrclc nroclilrciiri biochinricc. us()i"rrc slrLr nroclcralc. clcpcnclcntc clc doza
si i'cr clsibil,.: ia intrcrLlpcrcl tratanrcntului.
1\'!()l-{;l{.\\l()S'l'![{ (l)(]t) I)t'oclr-ts: l-lrL-r(,ON{AX (Schclinu l)lotrgh. Novariis. l:rrrtrprr )
- Iiotillzat si solLrtic pcntrll administretre parenterala;
cxista patrlr conccntratii: 150- 300: -100 si 700 mcg:
- indic:itiu nrrU()ra: rccluccrca ciLrralci ucr.rtropcuiilor sci'crc si e courplicatiilor
rue cstonr lu pacicntri strpr-rsi chinriotcrapici antiturnorale (cu cltct rnielosLlprcsor^

si rlce i si i'cciLrccrca risculLri clc inlcctic)- in spccial canccrul glandci manlzirc.

(:linccl' 0t irrian" tcslicirlar-. b|unho pulnronar- e tllo-rcctal. al r czicii irIinilrc.
prccrinr si Il 1'ueierrtii sLrpLrsi tlansplantulLri aLttolog dc maduva osoasa. pcntru a
lrceclcr.ir rclitcct'ca scnci rrricloiclc.
LI'.\*(X;ltASl'lN{ (l)CI) l)r'odusc: (ili.ANOCY'IL: (l{honc-Poulcnc. lruropa. Australia)
NI tl'l'lt(X;lN (('hLrgai. .laponia. China)
lltre oanc crr pultrcrc liolrlizata i srtlvct'tt. llcutru Lrtilizarc palcntcrala (s.c.. r.v. ):
indicatilr nrrrjorir: recluccrca durrrtci ncutlopcnici si a conrplicatiilor acliacente la
ir.rcientii cLr r"rcol"riazic ncnricloicla. prinritori ai unci auto-. sau alogrcf'e de maduva
()soirsA si Ia pacicntii cLr ncoplazic r-icnricloicla atlati in cursul Lrnor chinliotcrapii
cLrnose Lltc a 1i associr'itc cLl ncLltropcnie le brila.

/2
 /1ANA RI:(1 ) 11,1 1 TA
LL lLttlilti l it():)()II 11 tl
P()cstc capabiltl a sti11lLllC/Cl 11larca dc 81()b llc rosii atat la ol cat
)1

si ltl ccl ctl hclllat()p()icz l dclicitaral =anillnclc nornlalc

ill l)F / l]t lil)()cstc c()1lSidCrata tin llorlllon tistllal .cti strtlCt Lra 81icoprotcica,sccrctata
tl l illiclli.cti rasl tlin l llipoxia rc1lalal daca la tlnclc sl ccii dc 1lna11lilbrc ri1lichiul

Ci /ill itlill t11 t tl Sa l:I)()(calillc).l Cntr l tltc spccii(onl.SObola11.icpurc).s atl

(1 1 i tilt 1 tlitiri FCSI ()n abilc dc sccrcti l alccst li lhct()ri
)F()CIC hi()(chn()logiil() aLl pcl 11lis ca in tlltilllli 5-10 ani.sa nc prcci/ata structtlra
(1 11 i/( lttl 1l tl
P(
iCtil ci si
l sc()htina prin tchllica/ I)N rccolllbi1lant.r-111)()
itl (

(Cril () t)iCtin t lnlantl cc()n billata) ccCa cc a dcschis l10i pcrspcctivc tratal cntullli ullor
it) l) d
tllc1l lil.i1lcl oscbi dc ctiol()8ic lcllal l:
strticttlrilc chill icc si pl oprictatilc biolo3icc alc critropoictinclor obtinute dc la dil ritc
li dC in lllli lb c stlllt llcsclllllilicativ dilbl ite:
IDC

[)acl llt_ lp () 90-95(ll)din cI itl ()poictilla cstc silltctizata dc rillichi si 1luinai 5-10(/)cste
.a
l
1()(Itl 1 ll[ll
inal i11
l1ll ti 111 lrc Pal tC dC licat_d ll si dC CCILllCIC stcnl din nlad l

() ()tl

bit, `t:
illt / l l 1lal l
l1lP() l R)st illtcrpl ctttta dili_Nl it ill dcc lrsul tirllpultli.cxisttlnd lllai

liltl11 il)( tc/c tl tipr i 1 l tli lspcctl ipotc/ t pl od lccril dc I:l)()illtacta. ca atarc dc catl c

l11 l CI11l l)()pttlatillc ccl llarc ale rillichitlllli ca liasp ins la llipoxic.arc ill pl czcllt cci l ai
lll llti adcptil
- 1lI)() c silltcti/ca/ l clati conti11 lu la llivcl ll rinichiului si accasta datorita
llll)ttiltli ca il1 111()(l n()Fnlal C ista l l l i cl ll t lbil()r rcllali o starc dc hip()xic
r [lt i [1 hiP() ic dctcrllli11[lt lic dc aportul dc ox).8c1l dC la accst ni cl. 1lc dc
11 t111lLil illlrtll cnal ti
) :1:

S
l c10 dit xistcnta
lntli ritnl circadian al prod lctici dc l 1)()i astibl sc
il11 tistl ca/a al()1 i lllinilllc dilllincata(Orclc 8).()crcstcrc dc 42 ()la( rclc 16.si.
) lCI (lC ()()(I()ltt()1 ci 2()
l

ItP() tc si1licti/at l iln calltitati dc 2-411i/k3//i:

CCl ti l dc l:P()cstc tHl pl ()ccs transcriptional.detectat dupa 15-30 dc llninule dc

llil)() ic l :ltlltl: h()l 11()1ltll()dttt l pr()cltls ntl stc st()cat si cstc tl cctlt ill cil ctllatia
gcncr llal
11 i111 10a Stl lt cti 1/ lC Ctlrc I Ol dCtcrlllllla cl c L 1
C l prt)d lctici l cntllc cl 1lPO
( ll] 11111 acrtll atnl() lcric ctl prcsitinca () i8cntllLli SCa/ lta/ 1a altit ldini
11lal 1.

al cli()pttiilc c()118cnitale. 1lnsuliccnta puinlonara ctc). sau scadcrca ci

{ill lliccnttl llala clt)nica_ l) Fiti/iilc l cpctatc cLi Sa118c illtc Sa) xiStttnd() 1 11

t
[1lit: i:1 ) t))()1110n ll:l i11ll c concclltl
ttia l [l 1 ttictl clc hc11lo81obina si l

C llltililtc[l ti :)()lilllctionala l laSn3 lilcal

- 1)li}l il til[1 l lil)() stc stilllL:larCa critl ()poic/cil ccltllclc stclll plLirip()tcntc
lcti 111

CtlPti ilC tic tl c tli i/ t si

l sc dili_Nrcntitl. sc I ot tl a1lslk)li11la i1l pl cctlrsolli critrocitalli
t) l C lll litil lictl i sc dil FCntia/a stlb actit11lca t111()F lhCtOri hclllatopoictici dc crcstcrc
((: 1-(lSI_ll -3 s[1)II-3 l and tin l ()l prcl ondCrant in aparitia cclulclor critl ()citarC
l:)() sc li ca/tl pc rcccptorii spccilici prc/clnti pc ccltilc siclll si i1111 iclltca/ 1

nticrc l
(lilt lccSt( l slC lillia cl itroida. tlva1ld in f()l l ci1lscn 1lat ill lllaturarea
pltichctcl() [l11811i1lC s lti 111 111lltlcntttlrctl lcLICOp()1 /cl
( 11ll l C il l cl tl l l)F()dll(itici lil)(). c ist l11(1
il ()1lc hipOtalanlicc dc dctcctal e a
hipt) 1 i si ct)llti ol l)C Ctllc l oaSa t prod lctici rcilalc dc IJl)01

- plin tcirr)ologra ,,\i)N rcctimhirrant s-a obtinLrt I:.PO r-unana. rl lLrl jPO ALIrA (DCI)
rlir-rirl'O tlir l'A (lX'1)
indicaiiric tcrapcuticc alc rllLr l:l)0:
- lt'alantctttt-ti iLncntiei usociatc Lrnci insr-rllccntc rcnaIc cronicc. la pacienti aclLrlti si
c()ilii hclitoilializati" si la pacicr-rti adLrlti in dializ-a pcritoncala:
- tralantentul ancnrici scverc cle origir-rc rcnala, la pacientii adulti nedializati;
- lraluntcnlrLl ancnriei pacicntilor adulti clt cancer tratati cu chirnioterapice ( in
sltcci;Ll prociirsi clc platina):
tr.llarttcnLul lttrcnrici clctcnrinlitc dc iirlosirca ziciovuciinci la pacicntii cr-r SII)A:
- ltcltlt'Li crcstcrca proriLtctici cic sangc aLitolog la pacrcntir cc participa la rrn
l|c aul0Irtga.
i)t'r)!il'iir)) clc prcIe I
- ilttct'r cnlii ciriritt'gicaic progranratc e arc nce esitu o cantitatc ntarc clc sangc;
- tultturcntLrl pacicntilor cu o zrr-runie modcrata. lirra clcllcit cie fier (hematocrir i3-
: ii'r.
l)rrrcir.rsc:
il)i{l:X (()rtho. lrr-tropa. ('anacla. Australia). solutic proteica stcrila, tamponata,
ailntinistnlla s.c. siiLr i.r'.. contir-ianc1 cantrtati verriabile dc Ill'}O- AI.FA. dc 1000:
l0(X)" -l()0() si 10.000 Lr.i.\ml. intr'-o solutic cic scr albuminizat Lunan 0.25" .

I t)OI)llAl{ (.lulphar" Irrlirale le Arabc). sol.inj. cu 2000; 4000 u.i.}ll'}O-o

l.l'}l{l.X (('ilag. [:ii'ctia)-sol.inj. I000;2000: i000t'1000; 10000 r-r.i./ nrl.
\l.O I{l('OItNlON ([{ocirc. Anglia). sol. hrj. cu 500. 1000:2000:4000: -5000:
I0.000 u.i./r.r"rl r'-lIul-.PO B
\it,\\l SI) (,,\mgcri. l:Lrr"opa). sol.inj. dc dilcritc conccntratit. cunclitionatc in scringi
l)rcunrplutc. cr.rtic x 4 se rirrrli:
('(
Iti )it\{( )\- 1 I}ochrinrcr).
- dlloi.ilrr lcactiilol aclr,crsc gravc lclc tip:rnalilactic. cardiovascuial). aciministrarea se
rcitiizcaza rtutnai sLrb sirictit suprar,'cghcrc. r-rtilizarea grcsitn ar prociusr-riui sau in uxccs-
poatc provoca o crcstcrc cxccs:iva a hcmatocritr-rlr-ri" ceca cc poatc clctcl'rlina ef'ecte lir
niii-:l rascrriiu-. conrplicatii grarc. r.ru clc pr-ttinc ori scsizatc l:r sportivii care le rrtilizart".
Irdntlr.r ikrpitj. in vcdclcit crcstcrii pcrlirrmantclor