Mianserin inhibits disease progression, paw swelling, and interleukin-17 (IL-17) production in the collagen-induced arthritis (CIA) model of arthritis. DBA/1 CIA mice were therapeutically given an intraperitoneal injection of vehicle (phosphate-buffered saline,) or 10 mg/kg mianserin once a day for 7 days, starting on the day of disease onset. Mice were assessed for (a) clinical score (n = 20 mice per group) and (b) paw swelling on a daily basis (n = 15 to 17 mice per group). (c, d) Arthritis was scored histologically as described in Materials and methods for the vehicle control group (n = 18) and the mianserin-treated group (n = 17). (e) Mice were bled on day 7, and serum levels of IgG1 and IgG2a anti-collagen antibodies were measured (n = 20). Frames (a-e) show data pooled from three separate experiments. (f) On day 10 after disease onset, cells from draining inguinal lymph nodes were cultured and stimulated with bovine type II collagen (BCII) (50 mg/mL) or anti-CD3 monoclonal antibody (100 ng/mL) for 48 hours. Supernatants were analyzed for the production of interferon-gamma (IFNγ) and IL-17 by enzyme-linked immunosorbent assay. Each point represents an individual animal (n = 8). *P < 0.05, **P < 0.01, ***P < 0.001. unstim, unstimulated.