IFN-gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis

Siddiqui, AA; Brouwer, AE; Wuthiekanun, V; Jaffar, S; Shattock, R; Irving, D; Sheldon, J; Chierakul, W; Peacock, S; Day, N; White, NJ; Harrison, TS; (2005) IFN-gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis. Journal of immunology (Baltimore, Md, 174 (3). pp. 1746-1750. ISSN 0022-1767 DOI: https://doi.org/10.4049/jimmunol.174.3.1746

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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-gamma, TNF-alpha, and IL-8 were significantly higher in survivors compared with nonsurvivors. There were negative correlations between log TNF-alpha, IFN-gamma, and IL-6 levels and baseline cryptococcal CFU. Log IFN-gamma, G-CSF, TNF-alpha, 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-gamma remained independently associated with rate of clearance of infection. The results provide direct in vivo evidence for the importance of quantitative differences in IFN-gamma secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-gamma in the treatment of refractory HIV-associated cryptococcosis.

Item Type: Article
Keywords: HUMAN-IMMUNODEFICIENCY-VIRUS, TUMOR-NECROSIS-FACTOR, INTERFERON-GAMMA, VISCERAL LEISHMANIASIS, CEREBROSPINAL-FLUID, AIDS, SUSCEPTIBILITY, PATHOLOGY, GENETICS, DISEASE, Cryptococcus neoformans, growth & development, immunology, Granulocyte Colony-Stimulating Factor, biosynthesis, cerebrospinal fluid, HIV Infections, cerebrospinal fluid, drug therapy, immunology, mortality, Humans, Inflammation Mediators, cerebrospinal fluid, metabolism, Interferon Type II, cerebrospinal fluid, secretion, Interleukin-10, biosynthesis, cerebrospinal fluid, Interleukin-6, biosynthesis, cerebrospinal fluid, Interleukin-8, biosynthesis, cerebrospinal fluid, Meningitis, Cryptococcal, cerebrospinal fluid, drug therapy, immunology, mortality, Multivariate Analysis, Prognosis, Time Factors, Tumor Necrosis Factor-alpha, biosynthesis, cerebrospinal fluid
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Leishmaniasis Group
PubMed ID: 15661940
Web of Science ID: 226571300076
URI: http://researchonline.lshtm.ac.uk/id/eprint/6311


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