Immune mediators in cerebrospinal fluid during cryptococcosis are influenced by meningeal involvement and human immunodeficiency virus serostatus

Abstract

Pro- and anti-inflammatory mediators (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-8, IL-10, and soluble TNF receptor II [sTNFR] II) were measured in cerebrospinal fluid (CSF) before treatment (day 0), and after 2 weeks and 3 months of antifungal therapy in 51 human immunodeficiency virus (HIV)-positive and 7 HIV-negative patients with culture-confirmed cryptococcosis. On day 0, all mediator concentrations, except IL-10 in HIV-positive patients, were higher in patients with meningeal, rather than extrameningeal cryptococcosis or in control subjects (P < .05). For meningitis patients, all mediator levels, except sTNFR II, were higher in HIV-negative than HIV-positive patients (P < .05). Day 0 CSF IL-8 levels were higher in HIV-positive patients receiving antiretroviral therapy than in untreated persons (P < .02). Day 0 sTNFR II levels were higher in HIV-positive survivors at 3 months, and elevated levels were sustained in HIV-positive patients with meningitis. Overall, these data support the idea that inflammatory responses are crucial to the eradication of cryptococcal infections in the central nervous system.