Interleukin-1 and host control of pulmonary histoplasmosis

G. S. Deepe Jr.
Michael P. McGuinness, Philadelphia College of Osteopathic Medicine

This article was published in Journal of Infectious Diseases, Volume 194, Issue 6, Pages 855-864.

The published version is available at

Copyright © 2006 Oxford.


We found that interleukin (IL)-1ß levels were elevated in the lungs of mice infected with Histoplasma capsulatum. Hence, we examined the influence that IL-1ß and IL-1 signaling has on host defenses against pulmonary histoplasmosis. In IL-1 receptor 1 knockout (IL-1R-/-) mice challenged intratracheally, fungal recovery on day 7 after infection exceeded that in wild-type (WT) mice. Antibody neutralization of IL-1ß also exacerbated infection. For both groups of mice, the absence of bioactive cytokine led to a failure to control infection in a high proportion of mice. The absence of signaling had a modest effect on host resistance in mice with secondary histoplasmosis. Several perturbations in host defense mechanisms were detected in the lungs of IL-1R-/- mice. The number of CD4+ cells was decreased, and transcription of the gene for inducible nitric oxide synthase was depressed transiently. IL-4 and IL-10 levels were elevated in the lungs of IL-1R-/- mice, compared with those in the lungs of WT mice. Conversely, interferon-γ levels were decreased. Thus, IL-1 contributes to host resistance to infection with H. capsulatum. © 2006 by the Infectious Diseases Society of America. All rights reserved.