interleukin-8 and Meningitis--Cryptococcal

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.

Topics: Cryptococcus neoformans; Granulocyte Colony-Stimulating Factor; HIV Infections; Humans; Inflammation Mediators; Interferon-gamma; Interleukin-10; Interleukin-6; Interleukin-8; Meningitis, Cryptococcal; Multivariate Analysis; Prognosis; Time Factors; Tumor Necrosis Factor-alpha

A human immunodeficiency virus (HIV)-seronegative woman was admitted to the hospital with postpartum onset Cryptococcus neoformans var. gattii meningitis and markedly increased intracranial pressure. A poor initial response to antifungal therapy was followed, 2 months after hospital admission, by severe acute meningeal and cerebral inflammation and clearance of yeast cells from cerebrospinal fluid. This first reported case of paradoxical inflammatory reaction to C. neoformans illustrates important aspects of the host-pathogen interaction and highlights possible effects of immunomodulatory therapies.

Topics: Adolescent; Antifungal Agents; Brain; Female; HIV Seronegativity; Humans; Inflammation; Interleukin-10; Interleukin-8; Meningitis, Cryptococcal; Tumor Necrosis Factor-alpha

Cytokine levels were studied in the cerebrospinal fluid (CSF) of 16 adults with cryptococcal meningitis (CM). Low levels of tumor necrosis factor (TNF)-alpha and interferon-gamma, high levels of interleukin (IL)-1beta, IL-6, and IL-8, and the presence of IL-10 were documented. There were no significant differences in levels of TNF-alpha and interferon-gamma for CM and control patients. Mean CSF levels of IL-1beta (139.5 pg/mL), IL-6 (346 pg/mL), IL-8 (1160 pg/mL), and IL-10 (9.27 pg/mL) were significantly (P < .01) elevated in CM patients compared with levels in control patients. Despite the high CSF levels of IL-8, minimal leukocytosis was seen. Significant correlations between cryptococcal antigen titers and IL-10 levels (r = .8, P < .05), protein and cryptococcal antigen titer (r = .9, P < .05), and protein and IL-10 levels (r = .8, P < .05) were found.

Topics: Adult; AIDS-Related Opportunistic Infections; Cryptococcus neoformans; Cytokines; Humans; Interferon-gamma; Interleukin-8; Interleukins; Leukocytosis; Meningitis, Cryptococcal; Tumor Necrosis Factor-alpha

The contents of NO, TNF-alpha and IL-8 in the cerebrospinal fluids (CSF) of patients with tuberculous and cryptococcic meningitis were detected. The results showed that the concentration of NO2-/NO3- and the levels of TNF-alpha and IL-8 in CSF of the two kinds of meningitis were higher than those of normal CSF, and the concentration of NO2-/NO3- correlated positively to the content of TNF-alpha. The results indicate that the over production of NO, TNF-alpha and IL-8 in CSF may involve in the tissue inflammation and damage of central nerve system infection.

Topics: Adolescent; Adult; Child; Humans; Interleukin-8; Meningitis, Cryptococcal; Middle Aged; Nitric Oxide; Tuberculosis, Meningeal; Tumor Necrosis Factor-alpha