Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus afflicted mice

The objective of the this study was to determine the cytokine profile of aging mice and to establish whether changes in cytokine production account for the fact that aging mice develop a milder disease than the young in response to induced experimental systemic lupus erythematosus (SLE). Cytokine secretion was evaluated in groups of BALB/c and C3H.SW mice at different ages between 2 and 24 months. The production of IL-2, IL-4, IL-10, IFN gamma and TNF alpha was determined in supernatants of ConA-stimulated splenocytes and that of IL-1 in the supernatants of LPS-stimulated peritoneal macrophages. A gradual age-related decline was observed in the production of IL-2 and IFN gamma, whereas the levels of IL-4, IL-10, IL-1 and TNF alpha progressively increased with aging, in unimmunized BALB/c and C3H.SW mice. Experimental SLE was induced in 2 and 10 month old C3H.SW mice by immunization with the monoclonal anti-DNA antibody bearing the 16/6 Id. The characteristic cytokine profile following immunization of 2 month old mice was early increased production of TNF alpha and IL-1, followed by a peak of Th1 type cytokines (IL-2, IFN gamma). At a later stage of the disease, a peak of Th2 type cytokines (IL-4, IL-10) was observed that was concomitant with low levels of Th1 cytokines. In contrast, in the 10 month old mice that were immunized with 16/6 Id only a mild increase in all the above cytokines was observed. We suggest that the lower autoantibody production and moderate clinical manifestations in aging mice with experimental SLE are causally related to the decreased production of pro-inflammatory cytokines at the initial stages of the disease followed by a lower production of both Th1 and Th2 type cytokines.