LINKED IN-VIVO EXPRESSION OF SOLUBLE INTERLEUKIN-4 RECEPTOR AND INTERLEUKIN-4 IN MURINE SCHISTOSOMIASIS

Soluble interleukin-4 receptors (sIL-4R) are truncated IL-4R molecules that are secreted into biological fluids. To gain an insight into the mechanisms that control sIL-4R synthesis in vivo and their role in th e regulation of immune responses, the expression and secretion of sIL- 4R in mice infected with Schistosoma mansoni was studied. Splenocytes from infected animals responded to schistosomal antigen preparations w ith increased production of both IL-4 and sIL-4R. The synthesis of sIL -4R by spleen cells peaked at 8 weeks following infection and coincide d with maximum levels of sIL-4R in serum and sIL-4R-specific mRNA in t he liver of infected mice. The expression of IL-4-specific mRNA in the liver was different from that of IL-4R, reaching its peak approximate ly 2 weeks earlier. A relationship between sIL-4R production and the d evelopment and activation of Th2 cells was suggested by the findings t hat: (a) in vivo administration of anti-IL-4 antibodies (11B11) impair ed the ability of splenic cells to secrete either IL-4 or sIL-4R; and (b) splenic cells from mice vaccinated with irradiated cercariae,which tend to develop much weaker Th2 responses than mice injected with liv e cercariae, expressed reduced levels of sIL-4R when challenged with s chistosomal antigens. Moreover, a direct role for IL-4 in regulating t he expression of sIL-4R was suggested by the ability of anti-IL-4 anti bodies to inhibit sIL-4R synthesis in vitro. These data provide the fi rst evidence demonstrating that the production of sIL-4R in vivo is up -regulated during immune responses, especially during those characteri zed by the development and activation of Th2 cells and IL-4 secretion. The association between sIL-4R and IL-4 syntheses is consistent with a potential role for sIL-4R in the regulation of IL-4 activity in vivo .