FLS = fibroblast-like synoviocyte; ICAM = intercellular adhesion molecule; IFN = interferon; IP-10 = IFN-γ inducible protein-10; OA = osteoarthritis; PMN = polymorphonuclear neutrophil; PCR = polymerase chain reaction; RA = rheumatoid arthritis; RT = reverse transcription; SF = synovial fluid; Th = T-helper (cell); TNF = tumor necrosis factor. Abstract Chemokines play an essential role in the progression of rheumatoid arthritis (RA). In the present study we examined the expression and

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... mechanisms of IFN-γ inducible protein (IP)-10 in RA synovitis. RA synovial fluid contained greater amounts of IP-10 than did synovial fluid from patients with osteoarthritis. Immunolocalization analysis indicated that IP-10 was associated mainly with infiltrating macrophage-like cells, and fibroblast-like cells in the RA synovium. The interaction of activated leukocytes with fibroblast-like synoviocytes resulted in marked increases in IP-10 expression and secretion. Moreover, induction of IP-10 was mediated via specific adhesion molecules, as indicated by the finding that both anti-integrin (CD11b and CD18) and intercellular adhesion molecule-1 antibodies significantly inhibited IP-10 induction. These results suggest that IP-10 expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leukocytes with fibroblast-like synoviocytes, and that IP-10 may contribute to the recruitment of specific subpopulations of T cells (Th1 type) from the bloodstream into the synovial joints.