ROLE OF CYTOKINES IN RHEUMATOID ARTHRITIS

Abstract

▪ Abstract Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNFα, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cytokines such as IL-10 and TGFβ and cytokine inhibitors such as IL-1ra and soluble TNF-R. However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNFα and IL-1 produced. In rheumatoid joint cell cultures that spontaneously produce IL-1, TNFα was the major dominant regulator of IL-1. Subsequently, other proinflammatory cytokines were also inhibited if TNFα was neutralized, leading to the new concept that the proinflammatory cytokines were linked in a network with TNFα at its apex. This led to the hypothesis that TNFα was of major importance in rheumatoid arthritis and was a therapeutic target. This hypothesis has been suc...