title: Induction of tumor necrosis factor alpha by spherules of Coccidioides immitis.
abstract: The cytokine tumor necrosis factor alpha (TNF-alpha) functions as an immunomodulatory protein and as a mediator of cachexia. We report that viable or Formalin-killed spherules of Coccidioides immitis induced the secretion of TNF-alpha by peritoneal-exudate cells from BALB/c mice. The identification of the cytokine as TNF-alpha was based on its lytic activity against the TNF-alpha-sensitive LS murine fibrosarcoma cell line but not the TNF-alpha-resistant LR cell line, its neutralization by rabbit anti-TNF-alpha, and its secretion by peritoneal cells having characteristics of macrophages. The induction of TNF-alpha was to spherules and not to contaminating lipopolysaccharide (endotoxin), as evidenced by the finding that polymyxin B, a reagent that blocks the TNF-alpha-inducing component of lipopolysaccharide, did not negate the production of TNF-alpha in response to spherules, whereas pretreatment of spherules with hyperimmune goat antiserum to spherulin neutralized the induction of TNF-alpha by these cells. The demonstration that C. immitis activates macrophages to secrete TNF-alpha in vitro is a new finding and warrants studies to determine whether this cytokine is produced during active coccidioidomycosis.
authors.affiliation: Department of Research Immunology, San Antonio State Chest Hospital, Texas 78223.
authors.forename: D C
authors.initials: DC
authors.lastname: Slagle
authors.forename: R A
authors.initials: RA
authors.lastname: Cox
authors.forename: U
authors.initials: U
authors.lastname: Kuruganti
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000502:physiology; D000946:Antigens, Fungal / Q000276:immunology*; D001202:Ascitic Fluid / Q000378:metabolism; D003045:Coccidioides / Q000276:immunology*; D003046:Coccidioidin / Q000276:immunology*; D005260:Female; D006041:Goats; D007106:Immune Sera / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011112:Polymyxin B / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D007106:Immune Sera; D014409:Tumor Necrosis Factor-alpha; C009303:spherulin; D003046:Coccidioidin; D011112:Polymyxin B