In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. IL-4 mRNA, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymph nodes, and spleens of infected mice.

Using Northern Blot analysis, the endogenous levels of IL-4 and IL-2 mRNA in the spleens, mesenteric lymph nodes, and granulomatous livers of male CBA/J mice in the acute phase of infection with Schistosoma mansoni have been quantified. High levels of IL-4 mRNA were detected in all three tissues from infected mice, whereas none was detected in tissues from normal, uninfected, age-matched mice. Isolation of the granulomas from the livers of infected mice and subsequent extraction of total RNA from these lesions resulted in a 70-fold enrichment of IL-4 message compared with the whole, unseparated granulomatous liver tissue. Hence, the predominant source of the IL-4 mRNA detected in livers from infected mice appears to be the schistosome egg-induced granulomas within these livers. In contrast, IL-2 mRNA was never detected in any of these tissues from either infected or normal mice. Control experiments were performed that ruled out the possibility that this inability to detect IL-2 mRNA was due to a difference in the efficacy of the IL-4 and IL-2 probes or due to a selective lability of IL-2 message. These data imply that IL-4-producing, Th2 lymphocytes are active in and possibly integral to the granulomatous, delayed-type hypersensitivity response characteristic of this infection, and directly challenges the current hypothesis that delayed-type hypersensitivity responses are exclusively mediated by Th1 lymphocytes.