IL-1-induced inflammation promotes development of leishmaniasis in susceptible BALB/c mice

Elena Voronov, Shahar Dotan, Lubov Gayvoronsky, Rosalyn M. White, Idan Cohen, Yakov Krelin, Fabrice Benchetrit, Moshe Elkabets, Monika Huszar, Joseph El-On, Ron N. Apte

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


The role of host-derived IL-1 on the course of Leishmania major infection in susceptible BALB/c mice was assessed. Manifestations of the disease were more severe in mice deficient in the physiological inhibitor of IL-1, the IL-1 receptor antagonist (IL-1Ra) in comparison with control mice. In mice lacking one of the IL-1 genes (IL-1α or IL-1β), there was delayed development of the disease and more attenuated systemic inflammatory responses. IL-1α-deficient mice were slightly more resistant to L. major infection compared with IL-1β-knockout mice. During disease progression in IL-1Ra KO and control mice, myeloid-derived suppressor cells invaded the spleen, concomitant to suppression of T cell-mediated immunity and expression of systemic high levels of pro-inflammatory cytokines. In IL-1-deficient mice, Th1 responses were still apparent, even at late stages of the disease. Thus, dose-dependent effects of IL-1 were shown to influence the pathogenesis of murine leishamaniasis in susceptible BALB/c mice. Physiological and supra-physiological levels of IL-1 in the microenvironment promoted an exacerbated form of disease, whereas sub-physiological doses of IL-1 induced a less progressive disease. Thus, manipulation of IL-1 levels in the host, using the IL-1Ra or specific antibodies, has the potential to alleviate symptoms of visceral manifestations of leishmaniasis.

Original languageEnglish
Pages (from-to)245-257
Number of pages13
JournalInternational Immunology
Issue number4
StatePublished - 24 Feb 2010


  • Interleukin-1 receptor antagonist
  • Interleukin-1α
  • Interleukin-1β
  • Leishmaniasis
  • Pro-inflammatory cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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