Journal
CLINICAL INFECTIOUS DISEASES
Volume 39, Issue 9, Pages E83-E87Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/425121
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Background. Although Cryptococcus neoformans is a fungal pathogen that causes human disease predominantly in the immunocompromised host, severe cryptococcal infections are occasionally encountered in apparently immunocompetent individuals. Activation of cellular immunity by proinflammatory cytokines plays a central role in anticryptococcal defense. Methods. We describe 2 patients with severe cryptococcal meningitis who appeared to have idiopathic CD4 lymphopenia. For these patients and for 4 healthy volunteers, ex vivo stimulation of whole blood with microbial stimuli was used to investigate putative defects in cytokine production capacity. Results. Assessment of the cytokine released from the 2 patients with CD4 lymphopenia revealed a defective production of the proinflammatory cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF) but not of the anti-inflammatory cytokine interleukin-10 (IL-10). One patient with disease progression despite receipt of antifungal treatment was administered immunotherapy with recombinant IFN-gamma. Administration of recombinant IFN-gamma resulted in both restoration of immunological parameters and a sustained clinical recovery. Conclusions. Refractory meningitis may be due to defective TNF and IFN-gamma production, and IFN-gamma treatment may be useful in patients with an impaired cellular immune response and refractory cryptococcal meningitis.
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