Objective. To examine the molecular and cellular mechanisms in a model of a
cute inflammatory monarticular arthritis induced by methylated bovine serum
albumin (mBSA) and interleukin-1 (IL-1).
Methods. Mice were injected intraarticularly with mBSA on day 0 and subcuta
neously with recombinant human IL-1 beta on days 0-2. At day 7, knee joints
were removed and assessed histologically. Flow cytometry and RNase protect
ion were used to analyze IL-1-dependent events.
Results. C57BL/6 (B6), 129/Sv, and (B6 x 129/Sv)F-1 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 t
o disease. In contrast, B cell-deficient (mu MT/mu MT) mice developed arthr
itis at an incidence and severity similar to that of controls. ReIB-deficie
nt (ReIB-/-) 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 prote
in 2 (MIP-2), RANTES, MIP-1 alpha, and MIP-1 beta, in vivo and in vitro.
Conclusion. Arthritis induced by mBSA/IL-1 is strain specific and dependent
on CD4+ T lymphocytes and at least partially on ReIB, but not on B lymphoc
ytes or antibody. IL-1 contributes to leukocyte recruitment to the synovium
and directly induces chemokine mRNA production by synovial cells. This mod
el of acute monarticular arthritis is particularly suitable for further inv
estigations into cell-mediated immunity in arthritis and the role of IL-1.