Changes in the cytokine profile of lupus-prone mice (NZB/NZW)F-1 induced by Plasmodium chabaudi and their implications in the reversal of clinical symptoms

We have previously observed that aged lupus-prone (NZB/NZW)F-l (BWF1) mice when infected with Plasmodium chabaudi show an improvement in their clinica l lupus-like symptoms. In order to study the mechanisms involved in the lon g-lasting protective effect of the P. chabaudi infection in lupus-prone mic e we analysed specific aspects of the cellular response, namely the profile s of cytokine mRNA expression and cytokine secretion levels in old BWF1 mic e, in comparison with uninfected age-matched BWF1 mice and infected or unin fected BALB/c mice. Two months after infection, cells from BWF1 mice were s timulated with concanavalin A (Con A) and demonstrated a recovery of T cell responsiveness that reached the levels obtained with BALB/c cells. Old BWF 1 mice showed high levels of interferon-gamma (IFN-gamma) and IL-5 producti on and correspondingly low levels of IL-2 and IL-4 secretion before infecti on with P. chabaudi. Infection did not modify the IFN-gamma levels of BWF1 T cells, whereas it considerably increased the secretion of the Th2-related cytokines IL-4, IL-5 and IL-10. In addition, only BWF1 T cells showed incr eased mRNA expression of tumour necrosis factor-alpha (TNF-alpha) and trans forming growth factor-beta (TGF-beta). This counter-regulatory cytokine net work of infected BWF1 mice may be involved in the improvement of their lupu s symptoms. The results of our investigations using the complex model of P. chabaudi infection can be extended and, by using more restricted approache s, it may be possible to explain the multiple regulatory defects of lupus-p rone mice.