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.
OBJECTIVE: To examine the dose-specific effects of interleukin-12 (IL-12) on the evolution of murinetype 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.
Authors: Tram T Vuong; Sissel B Rønning; Henri-Pierre Suso; Ralf Schmidt; Kristian Prydz; Marlene Lundström; Anders Moen; Mona E Pedersen Journal: J Inflamm Res Date: 2017-07-04