Role of Inflammatory Cytokines in the Pathogenesis of Rheumatoid Arthritis and Novel Therapeutic Targets

Abstract

Cytokines are low molecular weight secreted proteins that mediate and regulate immune responses, inflammation and hematopoiesis; they act by autocrine, paracrine, endocrine and antagonistic mode of actions. cytokines have strong correlation with autoimmune disease, the most prominent among others is rheumatoid arthritis (RA) which targets synovial joints, and often accompanied by an array of extra-articular manifestations which are ultimately major predictors of increased morbidity and mortality, RA affect about 1% of the world population and about 0.6% of the American population with annual incidence estimated to about 40 per 100,000 individuals and mostly women. Persistent inflammation endorsed by major pro-inflammatory cytokines such as Interleukins (IL-1, IL-6) and tumor necrosis factors (TNF-α) and imbalance between the pro-inflammatory and anti-inflammatory cytokines is the main pathogenesis of RA. Evidence suggests that interaction between antigen-presenting cells and CD4+ T helper cells is involved in the induction of inflammation in RA. Continuous recruitment and activation of macrophages and monocytes occur with the recruitment of pro-inflammatory cytokines, specifically TNF-α, IL-1 and IL-6 into the synovial cavity resulting to loss of cartilage and bone erosion. These activated immune cells stimulate angiogenesis, which explains increased vascularity found in the synovium of patients with RA. Novel therapeutic targets are developed to minimize the morbidity rate, the use of TNF-α blockade drugs such as Adalimumab, Etanercept and Infliximab is widely approved globally with more precise therapeutic effect on inflammation. As the IL-1 plays a critical role in joint damage by facilitating the degradation of cartilage which leads to RA, the use of interleukin-1 receptor antagonist drugs such as Anakinra suppresses RA by inhibiting the release of IL-1, likewise, the use of anti-IL-6 receptor agent such as tocilizumab has become a major resource for the treatment of RA.