Modulation of Immune Responses in Murine Pulmonary Histoplasmosis

J Infect Dis. 1997 Apr;175(4):905-14. doi: 10.1086/513989.

Abstract

The influence of endogenous interleukin (IL)-12 on the course of pulmonary histoplasmosis was examined in naive and immune mice. All naive animals pretreated with anti-IL-12 monoclonal antibody (MAb) died by day 14. All mice died when anti-IL-12 MAb was initiated as late as postinfection day 3. Unlike those of controls, lungs of naive mice given anti-IL-12 MAb had depressed levels of interferon (IFN)-gamma and increased tumor necrosis factor (TNF)-alpha. The 2 groups had similar IL-4 levels. Administration of anti-IL-4 MAb rescued mice from the inimical effects of anti-IL-12 MAb. Survival of mice given both anti-IL-12 and anti-IL-4 MAb was associated with a blunted TNF-alpha response. In reinfection histoplasmosis, treatment with anti-IL-12 MAb did not alter survival. Fungus burden in lungs, livers, and spleens differed at week 2, but not at week 1, of infection. Thus, endogenous IL-12 is critical for optimal generation of a protective immune response in pulmonary histoplasmosis.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Cytokines / analysis
  • Histoplasmosis / immunology*
  • Histoplasmosis / pathology
  • Interleukin-12 / physiology*
  • Interleukin-4 / physiology
  • Lung / pathology
  • Lung Diseases, Fungal / immunology*
  • Lung Diseases, Fungal / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Rats

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • Interleukin-12
  • Interleukin-4