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Title: IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
Authors: Asna A. Siddiqui
Annemarie E. Brouwer
Vannaporn Wuthiekanun
Shabbar Jaffar
Robin Shattock
Diane Irving
Joanna Sheldon
Wirongrong Chierakul
Sharon Peacock
Nicholas Day
Nicholas J. White
Thomas S. Harrison
St George's University of London
Mahidol University
Radboud University Nijmegen Medical Centre
London School of Hygiene & Tropical Medicine
Nuffield Department of Clinical Medicine
Keywords: Immunology and Microbiology
Issue Date: 1-Feb-2005
Citation: Journal of Immunology. Vol.174, No.3 (2005), 1746-1750
Abstract: In animal models, immunity to cryptococcal infection, as in many chronic fungal and bacterial infections, is associated with a granulomatous inflammatory response, intact cell-mediated immunity, and a Th1 pattern of cytokine release. To examine the correlates of human immunity to cryptococcal infection in vivo, we analyzed immune parameters at the site of infection over time and assessed the rate of clearance of infection by serial quantitative cerebrospinal fluid (CSF) fungal cultures in 62 patients in a trial of antifungal therapy for HIV-associated cryptococcal meningitis. CSF IL-6, IFN-γ, TNF-α, and IL-8 were significantly higher in survivors compared with nonsurvivors. There were negative correlations between log TNF-α, IFN-γ, and IL-6 levels and baseline cryptococcal CFU. Log IFN-γ, G-CSF, TNF-α, and IL-6 were correlated positively with the rate of fall in log CFU/ml CSF/day. In a linear regression model including antifungal treatment group, baseline CFU, and these cytokines, only treatment group and log IFN-γ remained independently associated with rate of clearance of infection. The results provide direct in vivo evidence for the importance of quantitative differences in IFN-γ secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-γ in the treatment of refractory HIV-associated cryptococcosis.
ISSN: 00221767
Appears in Collections:Scopus 2001-2005

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