Abnormal Splenic and Thymic IL‐4 and TNF‐α 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‐a 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‐1α, IL‐6 and TNF‐a 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‐l/? 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‐α expression may predispose the development of autoimmune reactions. The expression of IL‐1ß and IL‐6 in the brain and kidney may be implicated in the damage of these two organs in MRL‐lpr/lpr mice.