To examine the molecular and cellular mechanisms in a model of acute inflammatory monarticular arthritis induced by methylated bovine serum albumin (mBSA) and interleukin‐1 (IL‐1).

Mice were injected intraarticularly with mBSA on day 0 and subcutaneously with recombinant human IL‐1β on days 0–2. At day 7, knee joints were removed and assessed histologically. Flow cytometry and RNase protection were used to analyze IL‐1–dependent events.

C57BL/6 (B6), 129/Sv, and (B6 × 129/Sv)F₁ hybrid mice, all H‐2^b strains, were susceptible to mBSA/IL‐1–induced arthritis, whereas C3H/HeJ (H‐2^k) mice were not. B6 mice lacking T and B cells (RAG‐1^−/−) or major histocompatibility complex (MHC) class II antigens (MHCII^−/−), and B6 mice treated with a CD4+ T cell–depleting monoclonal antibody, were resistant to disease. In contrast, B cell–deficient (μMT/μMT) mice developed arthritis at an incidence and severity similar to that of controls. RelB‐deficient (RelB^−/−) bone marrow chimeric mice had arthritis that was significantly reduced in incidence and severity. In B6 mice, flow cytometry demonstrated an IL‐1–dependent leukocyte infiltration into the synovial compartment and RNase protection assays revealed induction of messenger RNA (mRNA) for the chemokines monocyte chemoattractant protein 1, macrophage inhibitory protein 2 (MIP‐2), RANTES, MIP‐1α, and MIP‐1β, in vivo and in vitro.

Arthritis induced by mBSA/IL‐1 is strain specific and dependent on CD4+ T lymphocytes and at least partially on RelB, but not on B lymphocytes or antibody. IL‐1 contributes to leukocyte recruitment to the synovium and directly induces chemokine mRNA production by synovial cells. This model of acute monarticular arthritis is particularly suitable for further investigations into cell‐mediated immunity in arthritis and the role of IL‐1.