sitirhtrA diotamuehR

)AR(
otua cinorhc a si AR •
c ,enarbmem laivonys
otammalfni
ehtfonimrof
segnahc evitcurtsed ot sdael taht sitirhtrA diotamuehR
ecneserp htiw ,stnioj srotcaf diotamuehR ni )
.doolb eht
DhP ,ruodhK rehaM
ytisrevinU sduQ
lA -
m eht si sitirhtra hguohtlA •
a si siht taht derebmemer
c ti taht os smetsys

rhtrA diotamuehR sitirhtrA diotamuehR

ni noitairav ediW sitirhtra yrotammalfni
• fo mrof nommoc tsoM •
tesno ta ega –
tnemevlovni tnioj fo eerged – snoitalupop
stceffA lla1fo-2% •
esaesid fo ytireves –
selam > selameF 3 :1 •
e tciderp ot tluciffiD •
esaesid morf ega yna ta rucco yam tI eht tub
61 ,sraey
07
- •
morf si ecnedicni fo ega mumixam 03 .sraey
55
-

1
 ygoloitE AR fo stceffE
ammalfni cinorhc detaidem enummI •
:reggirT
setanimod tnemevlovni tnioj• tub esaesid cimetsyS •
latnemnorivnE ( citeneG 03)%
negitnA negitnA fleS
ytilatrom dna ytidibrom stceffa AR •
noitavitca llec T
ycnatcepxe efil secuder AR •
yb selam raey
7 –
noitammalfnI cinorhC yb selamef sraey
3 –
muivonys etartlifni sllec diohpmyL
muivonys ni mrof slessev doolb weN
noitarefilorp laivonyS
noitcurtsed tnioJ

suoremuN
ssecorP AR eht sisenegohtaP
:esnopser yrotammalfnI •
diotamuehR sexelpmoc enummI ( sexelpmoc enummi yb detaidem + ydobitna + negitna •
llec B erutpur LI
srotcaf stcudorp lairetcaB htiw
FNT
-1 ,
sisotycogahp
-cte
,
tnemelpmoc
hpromylop ecudni hcihw )
tna etycohpmyl namuh
LI -1 lamososyl fo esaeler dna )setycogahp( shpromylop eseht fo
llec T
fo rotaidem lacimehc eht sa tca hcihw sesaetorp dna semyzne
srotcaf elbuloS
tcerid dna
llec llec
– .noitammalfni
tcatnoc
negitnA - :egamad eussiT •
gnitneserp egahporcaM
sllec detavitcA .demalfni dna derujni suht si enarbmem laivonys •
setalumits hcihw ,I.nikuelretni esaeler enarbmem ni segahporcam
ro llec B
egahporcam gnigamad sesaetorp
LI dna
-1 dna snidnalgatsorp eterces ot stsalborbif
setycoivonyS FNT setycordnohC
sllec laivonys - fo aisalprepyH .enob dna egalitrac ,muivonys
sunnaP otni slacimehc gnigamad sesaeler hcihw ,sunnap secudorp
.enob yllautneve dna egalitrac gnidore os diulf laivonys

ralucitrA fo noitcudorP
dna esanegalloc
egalitrac sesaetorp
rehto
lartuen
.muehR
.W dnerA
sitirhtrA nimeS 1002 lppus(
03; 2:)1 -6 .

Interactions between numerous cells in the synovium, culminating in enzyme release and tissue damage, drive the process of
rheumatoid arthritis (RA).This shows some of the cells involved in the pathophysiology of RA. Individual cytokines may be produced by specific
cell types, although most cytokines can be synthesised by multiple cell types.,CD+ T cells are responsible for initiating and sustaining RA. The T
cell inappropriately recognises autoantigens (the HLA-DR antigen) on the surface of antigen-presenting cells. This causes activation of the T cell,
stimulating the release of cytokines that directly activate synovial macrophages.T cells also activate B cells, which release rheumatoid factors.
This leads to the formation of immune complexes, production of bacterial products, and the release of further proinflammatory cytokines that also
activate synovial macrophages.Activated synovial macrophages release large amounts of interleukin- (IL-) and tumour necrosis factor into the
synovium. These cytokines then stimulate synoviocytes and chondrocytes in the cartilage to release matrix metalloproteases, such as
collagenase and other neutral proteases, which degrade components of the cartilage matrix. Increased synoviocyte proliferation culminates in the
overgrowth of synovial tissue, known as pannus.IL- also plays a pivotal cytokine-mediating role in destruction of bone and cartilage in RA by
Arend WP. Cytokine imbalance in the activating osteoclasts to resorb bone. In addition, IL- causes impairment of bone and cartilage repair. .
Arend WP, Dayer J-M. Cytokines and cytokine inhibitors or antagonists pathogenesis of rheumatoid arthritis: the role of interleukin- receptor antagonist. Semin Arthritis Rheum. ;(suppl ):-. .

2
 sisenegohtaP
senarbmem laivonyS •
ra fo ecafrus fo snoisore sesuac sunnap laivonys ehT •
ys/egalitrac eht ta xetroc eht gnihcraeb yb & egalitrac
sore ehT .enob lairdnohcbus eht sedore ti ,snoitcnuj
mrof sezinagro sunnap ,retaL .citsyc & egral emoceb
sisolykna
( eussit suorbif ot gnidael
suorbif .)

.-:; .in rheumatoid arthritis. Arthritis Rheum

eloR latoviP aLIsyalP

-1 FNT
foLIrebmuN
dna
-1 
a evaH
-
yrotammalfnI
stceffE yrotammalfniorP gnippalrevO
AR fo sessecorP
LI -1 yrotammalfniorP yrotammalfniorP
LI fo stceffe -1 FNT fo stceffe -

setavitcA XOC -2
tsalborbif secudnI setavitcA setavitcA 
EGP
nogahporcam 
FNT - 2
/setyco noitarefilorp setycordnohc stsalcoetso 
ON

tsalcoetsO LI -1
sem noitavitca 
selucelom noisehdA 
htaed llec

cinegoignA 
senikomehC
srotcaf 
sesanegalloC
LI -6

sunnap laivonyS egalitraC enoB

noitamrof nwodkaerb noitproser
XOCepyt
olcyc
-esanegyxo
2= - nidnalgatsorp
EGP2 ; 2 = edixo cirtin = ON
-E 2;

3
arahC sI AR
noitcurtseD tnioJ
LAMRON AR
laivonyS :seludondemalfnI suoenatucbuS
laivonys
eht ni rucco yllausu •
enarbmem
enarbmem
eht no ylnommoc ,saera erusserp
,mraerof eht fo redrob ranlu suoenatucbus
:sepyt llec rojaM
setycohpmyl•T

sunnaP
segahporcam • tuoba ni poleved stneitap52
fo %
egalitraC :sepyt llec roniM
stsalborbif
•
sllec amsalp•
muilehtodne •
sllec citirdned
•

laivonyS
:epyt llec rojaM
eluspaC diulf slihportuen •

gninniht egalitraC
M nnamdleF morf detpadA lonummI veR unnA 6991
. 41
;793
: 044
- .
.

)tnioj PID( tnioj laegnalahpretni latsiD

tnemevlovni ralucitrA
tnioj PIP ,tnioj laegnalahpretni lamixorP
noitatneserp lacinilC
tnioj laegnalahpopracateM tnioj PCM ,

4
 sitirhtrA diotamuehR
vlovni ralucitrA smotpmyS
dna ,gnillews ,ssenffits ,niap edulcni AR fo smotpmyS •
AR nehW .stnioj elpitlum fo noitcnuf dna noitom fo snoitatimil
devlovni eb nac tnioj laivonys ynA gninrom ecneirepxe stneitap ,dellortnocnu ro evitca si
noitanimaxe tnioj no gnillews dna ,niap ,eugitaf ,ssenffits

acirtemmysa trats naC AR dellortnocnU fo smotpmyS cissalC

detceffa niap tnioj gniognO
eugitaf ro ssenffits gninrom tnacifingiS
sitivonys evitcA
,level PRC ro RSE eht fo noitavele tnetsisreP
egamad tnioj cihpargoidar ro

sitirhtrA diotamuehR tnemevlovni ralucitrA

serutaeF lacinilC
ni stnioj rehto ot sraey •ot shtnom nihtiw sdaerpS •
tcarahc si ssenffits eht – noitubirtsid lacirtemmys
d eht gnirud sevorpmi
sid eht fo ytivitca eht
sraey wef tsrif retfa uaetalp a sehcaer tnemevlovni tnioJ •
.ytivitca suounerts retfa
b detceffa stnioj lausu eht –
,stj laegnalahpopracatem ot detaler esaesid ylrae ni detceffa stnioj fo rebmuN •
.seot dna selkna esaesid fo ytireves

5
sitirhtrA diotamuehR sitirhtrA diotamuehR
raey ot shtnom reftA •
evah lliw siitrhtra diotamuehr hitw stneitap02
fo % •
era nommoc ,seludon suoenatucbus
sregnif eht fo noitaived ranlu –
hcihw ,yitmrofed kcen naws –
rucco nac ssenkaew dna eugitaf ,ssol thgiew •
a tnioj laegnalahpretni
tnioj
rofed ereinnotuob –
xorp eht fo noisnetxe dna tnioj
eenk eht fo yitmrofed –

6
sitirhtrA diotamuehR
sbaL •
,rotcaf
fo aresdiotamuehR
eht ni nees si ydobitna MgI na –
a diotamuehr htiw stneitap 57 fo %
aicossa era rotcaf diotamuehr
uof osla si rotcaf diotamuehR –
sitidracodne evitcefni ,silihpys
decnavda ni ;snoitcefni
.esaesid diotamuehr htiw stneitap

sitirhtrA diotamuehR sitirhtrA diotamuehR

airetirc fo
tnemtaerT desiveR
slaoG ygolotamuehR fo egelloC • naciremA •
;niap fo feiler
:sitirhtrA diotamuehR
–
fo sisongaid eht rof
;noitammalfni fo noitcuder – gniwollof eht fo ruof tsael tA –
> ssenffits gninroM ruoh
1 •
;sutats lanoitcnuf fo noitavreserp –
ylsuoenatlumis stnioj eerht ni sitivonyS •
c esaesid fo noitneverp –stnioj PIP ro PCM dnah ro tsirw ni sitivonyS •
dnaeht
)ydob ;egamad
fo sedistnioj
htob no saera tnioj emos( sitirhtra lacirtemmyS •
fo noituloser etelpmoc – seludon diotamuehR •
? rotcaf diotamuehr mureS naht ssel eb dluohs lamroN[ 04]lm/tinu
06
- •
sitirhtrA diotamuehR fo lacipyt segnahc cihpargoidaR •

7
ehT cigolocamrahP yparehT cigolocamrahP
D citamuehritnA
esaesiD
gniyifdoM
- •
a )sDRAMD( eht rof seitiladom cituepareht fo sessalc lareneg
4 •
nemtaerT eht rof :AR dehsilbatse fo tnemtaert
sDRAMD stnegA cigoloiB evitceles/)sDIASN(
itna ladioretsnoNsgurd yrotammalfni
- –
etaxertohteM tpecrenatE 1 esanegyxoolcyc ;srotibihni
-2
;sdiocitrococulG –
enizalasafluS bamixilfnI 1
;)sDRAMD( sgurd citamuehritna
esaesiDgniyfidom
- –
edimonulfeL bamumiladA 1
stnega lacigoloiB –
eniuqorolhcyxordyH arnikanA 2

enirpoihtazA tpecatabA 3
,rotibihni rotcaf sisorcen romuT1 nikuelretni
2 ,rotibihni
-1
,rotibihni noitalumitsoc 3llec
T- DC
B4 evitisop
02
- -rotibihni llec
-
eniropsolcyC bamixutiR 4

ehT cigolocamrahP yparehT cigolocamrahP

sreverri dna tsetaerG • eb dluohs DRAMD
tsrif eht nihtiw detrats fo tesno fo shtnom
3 •
esaesid sitirhtra diotamuehr fo smotpmys
emoctuo elbarovaf erom a ni stluser sDRAMD fo noitcudortni ylraE •
fi feiler citamotpmys rof desu eb yam sdioretsocitroc ro/dna sDIASN •
ylevissergga dna:suhT
ylrae taerT •
smotpmys ni tnemevorpmi dipar ylevitaler edivorp yehT .dedeen
erofeb shtnom ot skeew ekat yam hcihw ,sDRAMD htiw derapmoc
nemtaert elgnis oN • nees si tifeneb
noissergorp

8
muehritnA
esaesiD
gniyifdoM- yparehT cigolocamrahP
)sDRAMD( ot pu rof dewollof stneitap ni sDRAMD htiw tnemtaert ylraE 01 •
esaesid eht tuohtiw stneitap ot ralimis setar ytilatrom dah sraey

smotpmys lortnoC
evah ot detartsnomed neeb osla evah – taht stnega cigoloib ehT •
stceffe ciseglana etaidemmi oN itna
– eht edulcni ytivitca
esaesidgniyfidom
- ,tpecrenate( sgurd FNT
-
nikuelretni eht dna )bamumilada dna ,bamixilfni rotpecer
-1–
ht fo noissergorp yaled naC – .arnikana ,tsinogatna
tnioj wols/tneverp(
)noitcurtsed
n yllareneg stceffE –
shtnom

:sitirhtra diotamuehr htiw stneitap ni ytilatrom desaercni oN .la te ,HM kjiwsjiRnaV ,AM newueeLnaV ,JE toorK
siD muehR nnA .tesno esaesid morf pu wollof
ot pU fo sraey
01 0002 95
; 459: 859
– .

htrA diotamuehR SDRAMAD

oM esaesiD( tnemtaerT •
noc :etaxertohteM –
secudorp tI .AR ecno nevig si dna skeew
2 -6 taxertohteM –
od lausu ehT .ylkeew tsom ehT .keew a ecno
7 .551
- gm naht yrotammalfniitna erom eb thgim AR ni
nommoc
LI itna evah osla yam evisserppusonummi -1 a
rtsag si tceffe edis – senikotyc
ap ,yticixototapeh era
ot eud sesac ereves erom ni nesohc netfo si etaxertohteM
esoht naht semoctuo roirepus gnitseggus atad
gnol mret
-
stnegacigoloib naht tsoc rewol dna ,sDRAMD rehto htiw
.–

9
 avarA 
)edimonulfeL( 
)edimonulfeL(
avarA
taht gurd yrotaludomonummi –
smotpmys dna sngis secudeR gniitbihni•yb stceffe sit trexe yam
emyzne lairdnohcoitm eht
oj ot egamad larutcurts swolS •
dna ,)HDOHD( esanegordyhed etatoroordyhid
snoitcA • enisoryt fo noiitbihni
sesanik
vitareiflorpitnA
] noitacilpitlum dna htworg llec fo noiitbihni
[ –
gnol
yrotammalfni - evah ot sraeppa–edimonulfeL
itnAralimis ycaciffe mret
- •
evisserppusonummI – etaxertohtem fo taht sa

avarA 
)edimonulfeL( 
)edimonulfeL(
avarA

enizalasalfus ro etaxertohtem sa evitceffe sA •

a ecno :noitartsinimdA • dna sngis gnisaerced nI
smotpmys –
stceffe esrevdA • cihpargoidar gniwols nI
noissergorp –
aehrraiD ( noitca–fo tesno tsaf ylevitaleR )shtnom
1ot 2 •
hsar nikS –
ssol riaH – noitca fo noitarud deniatsuS •
myzne revil fo noitavelE –
egamad revil elbissop

10
 SDRAMAD REHTO avarA 
)edimonulfeL(
tnemtaerT •
doog a si enizalasafluS hitw stneitap rof dednemmocer
– toN •
iffe na htiw sitirhtra ycneicifedonummI –
na aineportuen edulcni stceffe
a na si enirpoihtazA –
redrosid worram enoB –
.sesac ereves fo esac snoitcefni dellortnocnu ,ereveS –
siht gnisu elihw dediova eb tsum ycnangerP •
noitacidem

htrA diotamuehR SDRAMAD

( enizalasalfuS
)dica cilasylasonimA
5 –
sisongorP •
dna yrotammalfniitna sit fo esuaceb )AR( rof desU •
ollof nac stneitaP ecneirepxe
05 57
- % – seiitvitca laiborcimitna
rof evitagenniera
noissimer
stneitap eseht( sraey
2
dna rotcaf diotamuehr )narumI( enirpoihtozA –
.)ytivitca esaesid gnirud tnasserppusonummI •
evah ohw stneitaP – ot ydob ehtorp
evitca eht ni detrevnoc
a si tI ,gurd
- •
eid egareva na no dna elpoep naht reilrae
01 51
sraey
- itbihni ot stca narumI
eitlobatem
.enirupotpacrem6-
ecniS .AR tuohtiw fo noitareiflorp eht rof yrassecen sisehtnys enirup
eitap eseht ,sraey owt setycohpmyl dna setycokuel yllaicepse ,sllec
.ylrae tnega gniyfidom

11
nerruC rotibihnI
FNT -α
FNT sdnib rotibihni
FNT -α sti stneverp dna -α •
srotpecer sti htiw noitcaretni
era emos ,seidobitna lanolconom era ynaM •
tpecrenatE•
snietorp noisuf rotpecer
amumiladA • FNT fo lavomer eht si laog citueparehT morf -α •
setis noitammalfni
bamixilfnI
• DRAMD a htiw noitanibmoc ni desU •
ro tceffe detcepxe( noitca fo tesno dipaR •
ni smotpmys devorpmi )skeew
1 -3

sroitbihnI FNT
sroitbihnI FNT ot sesnopseR srotibihnI FNT •fo sessalC
esnopser 06
laiitni
08
- % •
bamumilada :bAM namuH •
pord
0~1
raey -bamixilfni :bAM• namuh/eniruM
% rep ffo •
tpecrenate :rotpecer elbuloS
•
sesnopseR FNT oT emiT •
ecrenate rof shtnom
3 •
4ht rof )skeew
bamixilfni
~( esod 41 •

12
nikuelretnI
FNT fo stceffE esrevdA srotibihnI -α
esu ylno yllausU • snoitcaer etis noitcejnI –
gnisu retfa devorpmi lagnuf ro/dna ,lariv ,lairetcab fo- ksir desaercnI –
m yrotammalfni snoitcefni
stsinogatna noisserppus worram enoB –
ni gnitluser ,sgurd ot seidobitna fo noitareneG –
emit revo ycaciffe decuder
g eb ton dluohS •
supul
gurD
decudni- semordnys ekil
- –
eud stsinogatna FNT
srecnac niks dna amohpmyl fo ecnegremE –
ah taht snoitcaer gnol revo esu mret-

94

muzilicoT
LI sdnib gurD srotpecer
-6
bamuzilicoT
•
LI enikotyc stneverP rotpecer gnidnib morf-6 •
detibihni si noitacinummoc
lleC ot-llec
- bamuzilicoT
• :emaN cireneG •
oitcudorp stibihnI • armetcA :emaN dnarB •
stnioj eht ta noitammalfni esaerced ,rotibihni rotpecer nikuelretnI •
LI rof yllacificeps gnidnib
-6
htnom rep a no ylsuonevartni neviG •
sisab
yllausu :egasoD lm/gm
02 •
decuder fo ksir :edulcnI stceffE esrevdA •
fo ksir ,doolb ni level teletalp
noisnetrepyh
15 05

13
efaS :arnikanA arnikanA tereniK
( ):
noitcaer eits noitcejnI –
LI fo yitvitca cigoloib eht skcolb yleviittepmoc-1yb
tpecrenatE
ITRUhitw↑- – LI gniitbihni eht ot gnidnib
-1
aineportueN FNT hitw↑ tnega
- gnikcolB
- – nikuelretnirotpecer I epyt
-1
KP – desserpxe si hcihw
LI( ,)IR
-
1
3 /2 -s6rh –
T1 seussit fo yteirav ediw a ni
.snagro dna
yad a ecno: arnikanA
).c.s( ylsoenatucbus
001 gm –

eweN fo sutatS
scigoloiB reweN fo smsinahceM
bamixutiR
•
ni amohpmyl rof ADF
devorppa
- - 7991
,yraurbeF ADF
devorppa
- - 6002 rof
AR ereves yletaredom htiw stneitap
- noitelped •B
llec
-
ot esnopser etauqedani
- >1
sDRAMD
XTM htiw noitanibmoc ni esu
-
yrotalumitsoc fo noitibihnI
•
T( selucelom )lleC
-
ETADPU

tpecatabA
,rebmeceD ADF
devorppa
- - 5002 rof
AR ereves yletaredom htiw stneitap -
ot esnopser etauqedani - sDRAMD
>1
htiw ro yparehtonom sa esu -
sDRAMD
ETADPU

arnikananaht
ro stsinogatna
rehto FNT

14
 srotibihnI lleC
B- srotibihnI lleC
B-
bamixutiR • B tegrat yhW ?sllec
- •
suf/ciremihC – rotcaf diotamuehr fo noitcudorp rof ecnedivE
)FR( –
noc ydobitnA – GgI fo noiger cF ot sdnib hcihw ydobitnaotuA •
GgI namuh tnatsnoc
-1 fo noitcuder
B fo noitelpeD
yb deinapmocca si sllec
- –
rum dna snoiger noitammalfni
elbairav )esuom( devlovni sllec htiw tcaretni hcihw senikotyc eterceS –
snoiger esnopser enummiotua ni
elbairav esuoM • senikomehc
FNT .eI
dna ahpla
- •
tna morf emoc
DC sezingocer 02
B tegrat ot woH ?sllec
- •
cF ot sdnib oslA – DC 02 –
srotpecer B no ylevisulcxe dnuoF sllec
- •
slevel hgih ta desserpxE •

15
eM :bamixutiR noitcA fo msinahceM :tpecatabA

DC ot gnidnib yb esnopser enummi eht setaludom tpecatabA 08

DC/ 68
suht ,llec citirdned a sanegitna
hcus ,)CPA(
na nollec gnitneserp -
DC fo gnidnib yrotalumitsoc gnitneverp dna sllec T evian
82 no
T gnitaunetta.noitavitca llec
-

bamixutiR fo stceffE ediS

etaD ot slairT lacinilC AR ni neeS
bamixutir no snoitcefni ni esaercnI
•
stsinogatna FNT no snoitcefni ot ralimiS
-
tneuqerf erom
noisufnI
stneve
• detaler
-
srogir/sllihc/reveF
-
amedeoigna/sutirurp/airacitru/hsaR
-
aidracyhcat/noisnetopyH
-
msapsohcnorb/noitatirri taorhT
-
noisufni tsrif htiw nommoc eroM
•
esaerced yam noisufni dioretS
• ecnedicni

16