Cytokine patterns in a prospective cohort of HIV-infected patients with cryptococcal meningitis following initiation of antifungal and antiretroviral therapy

Cryptococcal meningitis (CM) is a life-threatening infection in HIV-infected patients, especially in resource-limited settings. Cytokine patterns in the cerebrospinal fluid (CSF) and sera may be related to clinical outcomes. This study aimed to evaluate cytokine patterns in the CSF and sera of HIV-infected patients with CM as well as the cytokines produced by peripheral blood mononuclear cells (PBMCs) when stimulated with LPS and cryptococcal GXM. CSF and serum levels of IL-2, IL-4, IL-8, IL-10, IL-12p40, IL-17A, INF-γ, TNF-α and CXCL-10 were measured in HIV-infected patients with CM (CM+ HIV+) at various time points. Cytokine levels were evaluated in the PBMC culture supernatants and the baseline values were compared to those of HIV-infected patients without CM (CM- HIV+) and healthy controls (CM- HIV-). CSF cytokine levels at admission (n = 33) were higher than levels among the 23 survivors at week 2, but statistically significant differences were observed for IL-8 and IFN-γ (p- HIV- individuals produced significantly higher levels of proinflammatory cytokines in response to LPS, with the exception of TNF-α, which showed higher levels among CM+ HIV+ patients. The PBMCs of CM patients produced higher levels of IL-4 than those of CM- HIV- patients in response to GXM stimulation, and levels progressively decreased during treatment (pCryptococcus neoformans will help to develop novel strategies to improve the outcomes of patients with cryptococcosis.