Synergistic effects of interleukin-1β and interleukin-17A antibodies on collagen-induced arthritis mouse model.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that mainly causes the synovial joint inflammation and cartilage destruction. Both interleukin-1β (IL-1β) and Interleukin-17 (IL-17) are important proinflammatory cytokines involved in the pathogenesis of RA. We investigated whether combination therapy with IL-1β and IL-17A antibodies would generate the potential for synergistic effects on a collagen-induced arthritis (CIA) mouse model. Mice with CIA were subcutaneously injected with humanized IL-1β antibody, IL-17A antibody, or combination treatment. The effects of treatment were determined by arthritis severity score, histological damage and bone destruction, autoreactive humoral and cellular immune responses and cytokine production. Treatment with IL-1β antibody or IL-17A antibody alone resulted in beneficial effects on clinical and histological parameters of CIA mice. Compared with the single antibody treatments, the combination therapy resulted in a more significant effect in alleviating the severity of arthritis by preventing bone damage and cartilage destruction, reducing humoral and cellular immune responses, and down-regulating the expression of IL-1β, IL-6, IL-17A, IFN-γ, RANKL and MMP-3 in inflammatory tissue. In conclusion, combination treatment with humanized IL-1β and IL-17A antibodies demonstrates synergistic beneficial effects for preventing joint inflammation and cartilage destruction and bone damage in CIA mice model. These studies also provide evidence that combination with IL-1β and IL-17A antibodies may lead to a new combinatorial therapy for RA patients.