Author/Editor		Ihan, Alojz
Title		Etiologija in patofiziologija revmatoidnega artritisa
Translated title		Ethiology and patophisiology of rheumatoid arthritis
Type		članek
Source		Farm Vestn
Vol. and No.		Letnik 55, št. Poseb št
Publication year		2004
Volume		str. 109-12
Language		slo
Abstract		Rheumatoid arthritis inflammation process is characterised by the production of soluble mediators with final alteration of cartilage and bone erosions. Etiological factors of RA remain obscure, but there is considerable evidence of a key role for CD4+ T cells in the pathogenesis of rheumatoid arthritis. Several attractive candidate antigens, mostly joint-specific, have been studied, but information regarding T cell responses to these antigens in patients is contradictory. Novel reagents (such as major histocompatibility complex and peptide tetramers) and sensitive techniques (such as intracellular cytokine staining) will aid in future studies to identify antigen-specific T cells. However mechanisms following CD4+ T cell activation are better understood: proinflam.natory cytokines belonging to innate as well as adeptive immunity are principal effectors. TNF alpha and IL1 beta are major components of the inflammatory process: TNF alpha is an important stimulus of cells producing inflammatory mediators (cytokines, metalloproteinases, NO, PGE2,...) and IL1 beta mediates cartilage and bone destruction (via secretion of metalloproteinases, decrease synthesis of glycosaminoglycans...). Progress in clinical practice has driven to market biological drugs targeted to inhibit TNF alpha and recently IL1 beta. Other cytokines taking place in the inflammatory cascade before TNF alpha and IL1 beta are potential future therapeutic targets such as IL18. Cytokines with anti-inflammatory effect (IL4, IL10, IL13...) can also be used for treatment of RA.
Summary		Za vnetje pro revmatoidnem artritisu je značilna sinteza topnih mediatorjev, ki povzročijo uničevanje sklepnega hrustanca in kostnine. Vzrok za nastanek RA ni znan, številne dokazi pa kažejo na poglavitno vlogo celic T pomagalk (CD4+) pri patogenezi bolezni. Med antigeni, ki naj bi sprožili aktivacijo celic T pomagalk, se najpogosteje omenjajo sklepni antigeni (napr. kolagen II), vendar rezultati niso zanesljivi. Novejše metode (napr. MHC-tetramerni reagenti) naj bi dali jasnejši odgovor tem. Bolje kot sprožilni antigeni so opredeljeni mehanizmi uničevanja sklepa, ki sledijo aktivaciji celic T pomagalk. TNF alfa in IL1 beta sta poglavitna mediatorja vnetja pri RA. TNF alfa stimulira celice, ki tvorijo vnetne mediatorje (citokine, metaloproteaze, NO, PGE2...), IL1 beta pa povzroča destrukcijo hrustanca in kostnine (prek izločanja metaloproteaz, zmanjšane sinteze glikozaminoglikanov...). Velik napredek pri zdravljenju RA so povzročila biološka zdravila, ki inhibirajo delovanje TNF alfa in IL1 beta. Tudi citokini, ki sodelujejo v vnetni kaskadi pred TNF alfa in IL1 beta (napr IL18) so laho tarča terapevtske inhibicije. Tudi citokini s protivnetnim učinkom (IL4, IL10, IL13) bi lahko bili učinkoviti pri zdravljenju RA.
Descriptors		ARTHRITIS, RHEUMATOID CYTOKINES CHEMOKINES