Journal Article

Two Patients with Cryptococcal Meningitis and Idiopathic CD4 Lymphopenia: Defective Cytokine Production and Reversal by Recombinant Interferon-γ Therapy

Mihai G. Netea, Annemarie E. Brouwer, Elizabeth H. Hoogendoorn, Jos W. M. Van der Meer, Marianne Koolen, Paul E. Verweij and Bart Jan Kullberg

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 39, issue 9, pages e83-e87
Published in print November 2004 | ISSN: 1058-4838
Published online November 2004 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/425121
Two Patients with Cryptococcal Meningitis and Idiopathic CD4 Lymphopenia: Defective Cytokine Production and Reversal by Recombinant Interferon-γ Therapy

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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)–γ 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-γ. Administration of recombinant IFN-γ resulted in both restoration of immunological parameters and a sustained clinical recovery.

Conclusions. Refractory meningitis may be due to defective TNF and IFN-γ production, and IFN-γ treatment may be useful in patients with an impaired cellular immune response and refractory cryptococcal meningitis.

Journal Article.  2714 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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