Publication: IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
Issued Date
2005-02-01
Resource Type
ISSN
00221767
Other identifier(s)
2-s2.0-19944432138
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Immunology. Vol.174, No.3 (2005), 1746-1750
Suggested Citation
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 IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis. Journal of Immunology. Vol.174, No.3 (2005), 1746-1750. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/16609
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Title
IFN-γ at the site of infection determines rate of clearance of infection in cryptococcal meningitis
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.