ABNORMAL SPLENIC AND THYMIC IL-4 AND TNF-ALPHA EXPRESSION IN MRL-LPR/LPR MICE

The MRL-lpr/lpr and MRL-++ mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-alpha expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-++ mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1 alpha, IL-6 and TNF-alpha in serum than MRL-++ mice, Interestingly, in MRL-lpr/lpr but not MRL-++ mice, the IL-6 concentration in culture supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand,IL-6 and IL-1 beta were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-++ mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-alpha expression may predispose the development of autoimmune reactions. The expression of IL-1 beta and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice.