Rheumatoid arthritis (RA) is a chronic, inflammatory, and destructive
polyarthritis with numerous autoimmune features and the potential for extra-articular
and systemic complications. Much progress has occurred in defining important
mechanistic components of RA, leading to significant advances in its treatment. RA is
a multifactorial and multistage disease, beginning with preclinical autoimmunity that
arises in a genetically predisposed individual who encounters one or more
environmental triggers, progressing to the clinical appearance of inflammation in joints
and sometimes in other organs, and leading to destruction of the articular cartilage and
adjacent bone. Regulatory role in inflammation, autoimmunity and articular destruction
in the joints of rheumatoid arthritis patients is played primarily by chemokines and
cytokines. Amongst many top players of inflammation in RA, tumour-necrosis factor-alpha (TNF-α) is counted as the chief culprit. It is produced by synovial macrophages,
B lymphocytes, and NK-cells. Furthermore, TNF-α has exhibited to be of particular
utility as a therapeutic target. IL-17A is synthesized by T helper 17 (Th17), which
initiates the generation of inflammation causing cytokines like interleukin-6 (IL-6), IL-8 and GM-CSF by cells of endothelium, epithelium and fibroblasts and localization of
neutrophils. Progression of inflammation in the synovial fluid is augmented by
chemokines in the joints of rheumatoid patients. Elevated levels of CC chemokines
(CCL2, CCL3, CCL4 and CCL5) and CXC chemokines (CXCL5, CXCL8, CXCL9
and CXCL10) have been reported in such patients. Moreover, these chemokines may
control cell trafficking directly by interacting with their cognate receptors present on
inflammatory cells and also by modulating angiogenesis. Several proinflammatory
cytokines and chemokines participate in many biological pathways finally setting the
loop of inflammation and exacerbation of the outcome and these serve as biomarkers
for a number of autoimmune and inflammatory disorders.
Keywords: Rheumatoid arthritis, Cytokines, Chemokine.
