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IL-1β is the pivotal cytokine and plays an important role in rheumatoid arthritis (RA).More recently,the biological therapy targeting this cytokine has been impressively effective for many RA patients.However, it remains insufficient in some patients.One of the reasons for these futures may be due to multiple cytokines involved in the disease process.In the present study, we constructed a single-chain bispecific antibody (scBsAb1/17) against both human IL-1β and human IL-1 7A which is mediator for several key cytokines involved in RA process such as TNF-α and IL-6.A number of in vitro assays demonstrated that scBsAb1/17 simultaneously bound to both targets with similar antigen-binding affinity as individual single-chain antibody molecule (anti-IL-1β scFv or anti-IL-17A scFv).Mice with collagen-induced arthritis (CIA) were administrated with either scBsAb1/1 7 or individual single-chain antibody alone, and noticed that treatment with scBsAb 1/17 significantly ameliorated clinical signs and alleviated histological lesion of CIA mice compared to treatments with anti-IL-1 β scFv or anti-IL-17A scFv alone.Production of C11-specific antibodies in scBsAb1/17 treated C1A mice was substantially lower than that of single-chain antibody-treated CIA mice.In addition, scBsAb1/1 7 was more potent in inhibition of collagen-specific proliferation of splenocytes and mRNA expression of TNF-o , IL-6,IL-2, IL-1β and IFN-γ in the spleen of CIA mice compared to single-chain antibody alone.These results suggest that scBsAb1/17 appears more beneficial in rheumatoid arthritis than monovalent single-chain antibody molecules.