Objective: To examine the dose-specific effects of interleukin-12 (IL-12) on the evolution of murine type II collagen-induced arthritis (CIA).
Methods: From day 24 through day 33 following primary immunization, mice received daily intraperitoneal injections of murine recombinant IL-12. Measurements of anticollagen IgG, cytokines, and corticosterone were performed using enzyme-linked immunosorbent assay and radioimmunoassay.
Results: CIA mice injected with a low dose of IL-12 (5 ng/day) exhibited accelerated onset and increased severity of arthritis. In contrast, administration of a high dose of IL-12 (500 ng/day) attenuated arthritic inflammation. The low dose of IL-12 induced tumor necrosis factor alpha (TNFalpha) production, whereas the high dose induced production of both IL-10 and corticosterone and suppression of anticollagen antibody levels. Administration of neutralizing anti-TNFalpha and anti-IL-10 antibodies reversed the dose-specific effects of IL-12.
Conclusion: IL-12 is an important immunomodulator during the pathogenesis of CIA. It appears to act by regulating humoral and cellular immune responses, as well as by mediating the expression of immunoregulatory cytokines and glucocorticoids.
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