TLR-2, TLR-3,TLR-4, TLR-8, and TLR-9 are mainly linked with RA pathogenesis.177 TLR-2 and MyD88 knockout mice were protectedfrom the development of joint swelling in streptococcal cell wall-inducedRA.178 Arthritis was also reduced in TLR-4and TLR-9 knockout mice.179 TLR-2 and TLR-9are expressed in synovial fibroblasts and induce the secretion ofIL-6 and IL-8.179 At the same time, TLR-4is associated with IL-17 secretion.180 TLRsare recognized as second hits in the inflammatory progression of theRA, with the first hit being citrullinated proteins, HLA-DR4, andrheumatoid factors/RF. This evidence concerns the gene CXCL8 and arthritic joint disease.