Cytokine induction in human coccidioidomycosis

To investigate the immune response to human infection with the fungus Coccidioides immitis, we measured cytokine production from peripheral blood mononuclear cells (PBMC) and plastic-adherent monocytes/macrophages (Mφ) isolated from healthy subjects who were skin test positive to spherulin, healthy subjects who were skin test negative, and patients with active coccidioidomycosis. PBMC and Mφ from all these donor groups secreted increased levels of tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in response to stimulation with formalin-killed spherules (FKS), as measured by enzyme-linked immunosorbent assays. Viable C. immitis spherules also stimulated PBMC and Mφ from healthy subjects and patients to secrete tumor necrosis factor alpha, interleukin-1β, and interleukin-6, although at levels lower than those induced by FKS. The production of these acute inflammatory cytokines may contribute to the immunopathogenesis of active coccidioidomycosis and could account for the toxicity of the FKS vaccine in humans.