COMPLETE PREVENTION OF THE CLINICAL EXPRESSION OF ADJUVANT-INDUCED ARTHRITIS IN RATS BY CYCLOSPORINE-A AND LOBENZARIT - THE REGULATION OF LYMPH-NODE CELL-POPULATIONS AND CYTOKINE PRODUCTION

A single dose of either cyclosporin-A (CsA) or lobenzarit (CCA) given with an arthrogenic adjuvant completely prevented expression of experi mental adjuvant arthritis in rats. The aim of this study was to unders tand how these drugs prevented the arthritis expression by studying th e popliteal lymph nodes draining the arthritic joints at various times after adjuvant injection. Neither drug affected the proliferation in popliteal lymph nodes at the time arthritis was normally expressed, ho wever, there was a marked change in the types of cells present. Immuno fluorescence assays showed a reduction in the proportion of CD4(+) cel ls, while the proportion of B-lymphocytes was almost doubled. This coi ncided with a marked elevation in the ability of these cells to produc e interleukin (IL)-6. At the same time production of other cytokines ( IL-2, tumour necrosis factor (TNF) and interferon (IFN)-gamma) was not greatly affected. However, one day after adjuvant injection IL-2 and IFN-gamma production was reduced. In vitro experiments showed that IL- 6 production by lymphoid cells was relatively unaffected by CsA and CC A but IL-2, TNF and IFN-gamma were suppressed by CsA. The results indi cate that CsA and CCA may modify the response to the arthritic adjuvan t by specifically inhibiting IL-2, TNF and IFN-gamma production at the time of adjuvant injection. The lack of inhibition of IL-6 by these d rugs reveals it may not play a key role in the initiation of this mode l of chronic inflammation.