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In vitro assays were used to characterize the role of these agents in host defense against Histoplasma capsulatum. Intracellular proliferation of H. capsulatum was measured in alveolar macrophages and peripheral monocytes of normal volunteers in the presence and absence of the TNF-\u03b1 antibody, infliximab. Both infliximab and control antibody enhanced fungal growth in monocytes and alveolar macrophages, suggesting this was a nonspecific antibody response. Despite similar intracellular fungal loads in the presence of both antibodies, lymphocyte proliferation in response to blood monocytes and alveolar macrophages infected with H. capsulatum was inhibited by the addition of physiologic doses of infliximab, whereas control antibody had no effect. The production of H. capsulatum\u2013induced interferon-\u03b3 and TNF-\u03b1 was assessed in 5-day cultures containing lymphocytes and alveolar macrophages or monocytes. Interferon-\u03b3 secretion was significantly reduced in the presence of infliximab. In summary, patients receiving anti\u2013TNF-\u03b1 therapy are at risk for developing disseminated histoplasmosis. This may be due to a defect in the TH1 arm of cellular immunity.<\/jats:p>","DOI":"10.1164\/rccm.200206-563oc","type":"journal-article","created":{"date-parts":[[2003,4,25]],"date-time":"2003-04-25T12:24:13Z","timestamp":1051273453000},"page":"1279-1282","source":"Crossref","is-referenced-by-count":201,"title":["Histoplasmosis after Treatment with Anti\u2013Tumor Necrosis Factor-\u03b1 Therapy"],"prefix":"10.1093","volume":"167","author":[{"given":"Karen L.","family":"Wood","sequence":"first","affiliation":[{"name":"Divisions of Pulmonary and Critical Care, and Infectious Disease, Department of Medicine and Department of Pediatrics, Infectious Disease, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chadi A.","family":"Hage","sequence":"additional","affiliation":[{"name":"Divisions of Pulmonary and Critical Care, and Infectious Disease, Department of Medicine and Department of Pediatrics, Infectious Disease, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth S.","family":"Knox","sequence":"additional","affiliation":[{"name":"Divisions of Pulmonary and Critical Care, and Infectious Disease, Department of Medicine and Department of Pediatrics, Infectious Disease, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin B.","family":"Kleiman","sequence":"additional","affiliation":[{"name":"Divisions of Pulmonary and Critical Care, and Infectious Disease, Department of Medicine and Department of Pediatrics, Infectious Disease, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna","family":"Sannuti","sequence":"additional","affiliation":[{"name":"Divisions of Pulmonary and Critical Care, and Infectious Disease, Department of Medicine and Department of Pediatrics, Infectious Disease, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Day","sequence":"additional","affiliation":[{"name":"Divisions of Pulmonary and Critical Care, and Infectious Disease, Department of Medicine and Department of Pediatrics, Infectious Disease, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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