IFN-α downmodulates initial activation and subsequent antigen-induced reactivation of proinflammatory cytokines but enhances the initial activation and prevents subsequent antigen-induced inhibition of TGF-β reactivation. Mice were immunized twice with mBSA plus IFA with or without IFN-α at 1-week intervals followed by intraarticular injection of mBSA in PBS 21 days later. Levels of IL-1β, IL-6, IL-12, IL-17, TNF, IFN-γ, IL-10, and IL-13 were determined by Luminex, and TGF-β, by ELISA in serum collected at days 0, 14, 21, and 28 during the course of AIA. Data are expressed as mean pg/ml ± SEM (n ≥ 6). The black line, blue line, and red line represent groups receiving 0 U, 1,000 U, and 5,000 U of IFN-α, respectively, at the time of mBSA immunizations. Mann–Whitney U test was performed to compare cytokine levels between two groups. Animals not receiving intraarticular injection of mBSA (the dotted line) produced significantly (P < 0.05) less of all analyzed cytokines at day 28 compared with the control group. *P < 0.05 between PBS (black) and IFN-α 1,000 U (blue). #P < 0.05 between PBS (black) and IFN-α 5,000 U (red). The experiment was performed twice with similar results.