ROLE OF IL-2 AND IL-4 IN EXACERBATIONS OF MURINE ANTIGEN-INDUCED ARTHRITIS

In this study the roles of different T-cell subsets, and produced cyto kines, were investigated in an animal model for acute exacerbations. F lare-up reactions are inducible in the chronic phase of a smouldering antigen-induced inflammation by injection of a small amount of an anti gen into a hyper-reactive knee joint. In vivo treatment with anti-CD4 monoclonal antibodies (mAb) almost totally blocked the flare reaction, whereas anti-CD8 treatment did not exert any effect. The role of T-he lper 1 (Th1) cells in delayed-type hypersensitivity-resembling disease s is generally entitled proinflammatory, whereas Th2 cells act in an a nti-inflammatory manner. To investigate the role of these T-cell subse ts in flare-up reactions, anti-interleukin-2 (IL-2) and anti-IL-4 mAb treatments were performed. Anti-IL-2 treatment partly blocked the flar e reaction, and anti-IL-4 treatment, although the result was unexpecte d, blocked the flare more efficiently. Furthermore, when human recombi nant IL-2 (hrIL-2) and murine recombinant IL-4 (mrIL-4) were co-inject ed with the antigen to test their ability respectively to potentiate o r down-regulate the flare reaction, both cytokines demonstrated additi onal pro-inflammatory effects, although hrIL-2 was more potent than mr IL-4. The mere effect of hrIL-2 and mrIL-4 was studied by direct injec tion into a hyperreactive joint. No flare-up reaction or cell-influx c ould be induced, suggesting that other mediators are needed to exert p ro-inflammatory effects of IL-2 or IL-4. We conclude that not only Th1 cells, but also Th2 lymphocytes (at least regarding IL-4 production) may play a pro-inflammatory role in flare-up reactions of chronic arth ritis. Considering therapeutic application of Th2 cell-derived cytokin es, one should be aware of the possible pro-inflammatory potential of IL-4.