Inhibition of TNF-alpha secretion by methylxanthines - beneficial effect of immune complex nephritis in SLE-prone MRL-1pr/1pr mice

The derivative of methylxanthines, pentoxifyllin (Ptx), was recently described to inhibit the effect of TNF-alpha on granulocytes and was used in patients suffering from ARDS. Since elevated plasma levels of TNF-alpha and IL-1 are features of the SLE in MRL-lpr/lpr mice developing immune complex nephritis and vasculitis, 3 months old female MRL-lpr/lpr mice were treated for 3 month with PBS or two different concentrations of Ptx two times daily. Under this therapy the PBS treated mice developed a full blown immune complex nephritis characterized by a massive proteinuria, while those mice treated with Ptx showed no or only a slight increase in proteinuria or other symptoms of the SLE. Further, the PBS treated mice developed massive enlargements of all lypmphatic organs, while the Ptx treated mice showed a clearly reduced lypmphoproliferation as monitored by size of lymphnodes and spleen. However, in comparison to normal mice, there was still an enlargement of submandibular, paraaortal a nd superficial inguinal lymphnodes in these mice. Therefore, the beneficial effect of Ptx on the course of the disease, especially on the immune complex nephritis, indicates another promising application of this drug in the clinics.