IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis.
IL-10 has anti-inflammatory and immunoregulatory properties that suggest a potential therapeutic role in RA. IL-10 inhibits proinflammatory cytokine and chemokine production in addition to blocking T-cell responses to specific antigens. It acts primarily through inhibition of costimulatory properties of macrophages. IL-10 stimulates proliferation and differentiation of antibody-forming B-cells. Preclinical studies in a variety of animal models, including collagen-induced arthritis, have shown that IL-10 is effective in preventing or inhibiting inflammation and autoreactivity. Although in RA, circulating and synovial levels of IL-10 are increased, accumulated evidence suggests that there may be a relative deficit of available IL-10. Moreover, exogenous addition of IL-10 in vitro has been shown to affect the immunopathological processes involved in RA. Preliminary studies of human recombinant IL-10 in patients with RA have demonstrated a trend towards efficacy with a good safety profile. Taken together, the data support a therapeutic role for IL-10 in the treatment of RA.
Keystone
E
E
Centre for Advanced Therapeutics, Mount Sinai Hospital, Toronto, Ontario, Canada.
Wherry
J
J
Grint
P
P
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D013582:Synovial Fluid
D011994:Recombinant Proteins; D016753:Interleukin-10