Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients

Clin Exp Immunol. 2021 Oct;206(1):82-90. doi: 10.1111/cei.13644. Epub 2021 Aug 8.

Abstract

The roles of cytokines and chemokines in HIV-associated cryptococcal meningitis (HCM) and HIV-associated tuberculous meningitis (HTBM) are debatable. In sum, 34 HIV-infected patients without meningitis, 44 HCM patients and 27 HTBM patients were enrolled for study. The concentrations of 22 cytokines/chemokines in cerebrospinal fluid (CSF) were assayed at admission. Principal component analysis (PCA), Pearson's and logistic regression analyses were used to assess the role of cytokines/chemokines in HCM and HTBM. We found the levels of T helper (Th)17, Th1 [interleukin (IL)-12p40, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and TNF-β and Th2 (IL-2/4/5/6/10)] cytokines were elevated in patients with meningitis compared with those in HIV-infected patients without central nervous system (CNS) infection. Furthermore, the IL-1Ra, IL-12p40, IL-17α and monocyte chemotactic protein-1 (MCP-1) levels were higher in HCM patients, while the IFN-γ, regulated upon activation, normal T cell expressed and secreted (RANTES) and interferon-inducible protein-10 (IP)-10 levels were higher in HTBM patients. Elevated CSF concentrations of IL-17a, TNF-β, IL-5, IL-12p40 and IL-1Rα were closely related to meningitis, but elevated IP-10, MCP-1, RANTES and IFN-γ levels and CSF white blood cells (WBCs) were protective factors against HCM. Our study suggested that HIV-infected patients with low CSF WBCs have a high risk of HCM. Th1, Th2 and Th17 cytokines/chemokines mediate differences in the pathogenesis of HCM and TBM. Overexpressed proinflammatory MCP-1, RANTES, IFN-γ and IP-10 in CSF are protective factors against HCM but not HTBM.

Keywords: Cryptococcus; HIV; chemokine; cytokine; meningitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokines* / cerebrospinal fluid
  • Cytokines* / immunology
  • Female
  • HIV Infections* / cerebrospinal fluid
  • HIV Infections* / complications
  • HIV Infections* / immunology
  • HIV-1 / immunology*
  • Humans
  • Male
  • Meningitis, Cryptococcal* / cerebrospinal fluid
  • Meningitis, Cryptococcal* / etiology
  • Meningitis, Cryptococcal* / immunology
  • Middle Aged
  • Tuberculosis, Meningeal* / cerebrospinal fluid
  • Tuberculosis, Meningeal* / etiology
  • Tuberculosis, Meningeal* / immunology

Substances

  • Cytokines