Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF inhibition by an anti-TNFα monoclonal antibody and by pentoxiphylline

We have previously shown that the clinical manifestations of experimental systemic lupus erythematosus (SLE) correlate with an early increased secretion of TNF alpha and IL-1. In the present study, we examined the efficacy of two therapeutic modalities which lower TNFa production or activity, on the clinical manifestations of the disease. Experimental SLE was induced in naive C3H.SW mice by injection of the human anti-DNA monoclonal antibody (mAb) bearing the common idiotype, 16/6 Id. Two weeks after booster injections, treatment with either an anti-TNF alpha mAb, or pentoxiphylline (PTX) was started, for a period of 6 weeks. Production of TNF alpha (by splenocytes) and IL-I (by peritoneal macrophages) was determined 3 and 7 months after disease induction. The experimental mice were also followed for disease manifestations. Both treatment protocols, with anti-TNF alpha mAb and with PTX, reduced the production of the two pro-inflammatory cytokines, TNF alpha: and IL-1, in mice with experimental SLE. Anti-DNA antibodies were significantly lower in the mice treated with either protocol. In addition, a significantly lower rate of leukopenia, proteinuria and immune complex deposition was observed in treated mice. Abrogation of TNF alpha and IL-1 production in the early stages of experimental SLE by an anti-TNF alpha mAb or by PTX improves the clinical status of mice afflicted with this autoimmune disease.