Figure 1.

Schematic representation of the interleukin families and receptors involved in the pathogenesis of rheumatoid arthritis. Only those interleukins and interleukin (IL) receptors are shown where studies have demonstrated positive association between genes/SNPs and disease phenotype. Interleukins are assigned to each family based on sequence homology and receptor chain similarities or functional properties, considerable overlap between these families exists. Polymorphisms in genes encoding ILs and ILRs have been found to be involved in rheumatoid arthritis. Ligand binding initiates intracellular phosphorylation cascades that are mediated by kinases [i.e., interleukin 1 receptor associated kinase (IRAK); mitogen-activated protein kinase (MAPK); Janus kinase (JAK) and tumor necrosis factor (TNF) receptor associated factor, TRAF], resulting in signal transduction through certain transcription factors [including signal transducers and activators of transcription (STAT); nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)]. These transcription factors stimulate the expression of a number of pro-inflammatory and anti-inflammatory cytokine genes involved in the pathogenesis of rheumatoid arthritis.