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

Int Immunol. 2010 Apr;22(4):245-57. doi: 10.1093/intimm/dxq006. Epub 2010 Feb 24.


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-1alpha or IL-1beta), there was delayed development of the disease and more attenuated systemic inflammatory responses. IL-1alpha-deficient mice were slightly more resistant to L. major infection compared with IL-1beta-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, T(h)1 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Disease Susceptibility
  • Inflammation / pathology
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology*
  • Interleukin-1alpha / deficiency
  • Interleukin-1alpha / genetics
  • Interleukin-1beta / deficiency
  • Interleukin-1beta / genetics
  • Leishmania major*
  • Leishmaniasis, Cutaneous / genetics
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout


  • Interleukin-1
  • Interleukin-1alpha
  • Interleukin-1beta