Interleukin-1 and Host Control of Pulmonary

We found that interleukin (IL)–1b levels were elevated in the lungs of mice infected with Histoplasma cap-sulatum. Hence, we examined the influence that IL-1b and IL-1 signaling has on host defenses against pul-monary 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-1b 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-g levels were decreased. Thus, IL-1 contributes to host resistance to infection with H. capsulatum. Infection with Histoplasma capsulatum is common in the midwestern and southeastern parts of the United States. Most infected individuals do not seek medical care, either because they are asymptomatic or because they have only a mild, influenza-like illness. After an individual is exposed by inhalation, the organism un-dergoes intracellular replication within monocytes and macrophages in the lungs until cellular immunity is activated to arrest growth. The failure of the host to restrict replication of the fungus leads to a progressive infection in which multiple visceral organs and the bone marrow are involved [1]. Progressive infection may de-velop after either reinfection or reactivation. The con