Endogenous interleukin 12 (IL-12) regulates granuloma formation induced by eggs of schistosoma mansoni and exogenous IL-12 both inhibits and prophylactically immunizes against egg pathology

Academic Article

Abstract

  • Morbidity in humans infected with Schistosoma mansoni results primarily from the deposition of parasite eggs in portal areas where they induce a granulomatous response. In mice infected with this helminth granuloma formation is a CD4+ T helper (Th) cell-dependent process that is associated with a strong Th2 cytokine response which appears to evolve through a Th0 phase. In this report, we asked whether endogenously synthesized or exogenously induced interferon (IFN)γ through its suppression of Th2 cell expansion exerts a regulatory role on egg pathology. Depletion of IFN-γ or natural killer cells resulted in a marked enhancement of granuloma formation around intravenously injected eggs and was associated with increased Th2 and decreased Thl and interleukin (IL)12 mRNA expression. Similar changes occurred when egg-injected mice were treated with neutralizing monoclonal antibodies specific for IL-12 indicating a role for this cytokine in the regulation of the granulomatous response. In contrast, treatment with exogenous rlL-12 profoundly inhibited primary granuloma formation while increasing IFN-γ IL-2, IL-10, and IL-12 pulmonary mRNA levels and suppressing IL-4, IL-5, IL-6, and IL-13 mRNA expression. Cytokine depletion studies indicated that the effects of IL-12 could be attributed primarily to increased IFN-γ Importantly, IL-12 also inhibited secondary granuloma formation in mice presensitized with eggs demonstrating a role for the cytokine in reversing established Th2-type responses. Moreover, mice sensitized with eggs in combination with IL-12 to precommit them toward a Thl response developed only minimal granulomas upon subsequent egg challenge. The latter findings suggest that simultaneous vaccination with antigen plus IL-12 may provide a strategy for the prevention of schistosome egg pathology as well as other diseases stemming from Th2 cytokine production. © 1994, Rockefeller University Press., All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Wynn TA; Eltoum I; Oswald IP; Cheever AW; Sher A
  • Start Page

  • 1551
  • End Page

  • 1561
  • Volume

  • 179
  • Issue

  • 5