| Summary: | In RA (and in collagen-induced arthritis in DBA/l mice) experimental evidence has convincingly demonstrated the therapeutic benefit of anti-TNF-α antibodies, whereas anti-TNF-α also induces lupus-associated DNA antibodies in a minority of presumably genetically susceptible individuals, and accelerates SLE nephritis in NZB/W mice whose disease is suppressed by anti-IL-10. Conversely, TNF-α replacement protects NZB/W F1 mice from developing SLE, as does anti-IL-10 therapy, by inducing TNF-α. Likewise, IL-10 accelerates lupus and production of DNA antibodies in NZB/W F1 mice but is partially protective in collagen II-induced arthritis and may ameliorate RA by reducing TNF-α production. The discussion would be incomplete without reference to the observation that IFN-γ treatment has occasionally induced SLE in RA patients [17]. Paradoxically it has been noted that monoclonal anti-IFN-γ accelerates autoimmunity in NZB/W F1 mice [23]. These conflicting findings do not allow a firm conclusion on the role of IFN-γ in SLE, but in RA at least, exogenous (excess) IFN-γ appears to occasionally promote the development of SLE. It is likely that the restored lymphocyte response we have observed in RA patients treated with anti-TNF-α is associated with normalization of IFN-γ production [11]. This restoration of IFN-γ production by activated T cells using anti-TNF-α therapy could additionally contribute to the induction of lupus in the patients in our study, although this is difficult to rationalize with current immunological ideas. In extrapolating these emerging concepts from trials of immunotherapy, we hypothesize inverse roles for the cytokines TNF-α and IL-10 (to which IL-4 could also be theoretically added) in RA and SLE. We would speculate that whereas blockade of TNF-α is beneficial in RA, it may prove harmful in SLE. Similarly, anti-IL-10 antibodies may be a logical therapy in SLE but could be harmful in RA. Exogenous administration of IL-10 (and IL-4), it might be argued, could be beneficial in RA but harmful in SLE. These predictions can initially be tested in animal model systems, but can ultimately only be proven by experimental interventions in man. Such interventions might support our contention that, as far as cytokine pharmacology is concerned, what is good for RA is not necessarily good for SLE. © 1994 Springer-Verlag.
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