Clinical characteristics and expression of Th1-Th2 cytokines in the cerebrospinal fluid of patients with cryptococcal meningitis

Abstract

Background Cryptococcal meningitis (CM) is the most common fungal infection of central nervous system, caused by Cryptococcus neoformans infection of the meninges. The development and prognosis of CM depend on the patient's own immune function to some extent, and are relative to the imbalance of helper T lymphocyte (Th1/Th2). This study aims to explore the hidden role of the local Th1/ Th2 immune response in the pathophysiological process of CM.  Methods The levels of Th1 cytokines interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and Th2 cytokine interleukin-10 (IL-10) in the cerebrospinal fluid (CSF) were detected by enzyme-linked immunosorbent assay (ELISA). CSF cytology changes were monitored dynamically to understand the outcome status of patients with CM.  Results The levels of IFN-γ and TNF-α in CM patients [(11.17 ± 1.50) and (18.74 ± 2.97) pg/ml, respectively] were significantly lower than that in control patients [(17.69 ± 2.34) and (28.83 ± 3.55) pg/ml; P = 0.000, for all]. However, the levels of IL-10 in CM patients [(43.65 ± 10.12) pg/ml] were significantly higher than that in control patients [(7.80 ± 1.30) pg/ml, P = 0.000]. The CSF IFN-γ and TNF-α levels in acute phase of CM patients [(11.17 ± 1.50) pg/ml and (18.74 ± 2.97) pg/ml, respectively] were significantly lower than that in stable phase of CM patients [(17.70 ± 2.34) and (22.93 ± 1.53) pg/ml; P = 0.000, for all]. On the other hand, the levels of IL-10 were significantly higher in the acute phase than that in stable phase [(43.65 ± 10.12) and (22.93 ± 7.39) pg/ml, respectively; P = 0.000]. The ratios of Th1/Th2 were used to assess the contribution of Th1/Th2 immunity in acute and stable phase of CM patients. The ratios of IFN-γ/IL-10 and TNF-α/IL-10 measured in acute phase of CM patients were significantly lower than that in control patients (P = 0.000, for all). These ratios in acute phase patients were also significantly lower than that in stable phase patients (P = 0.000, for all).  Conclusions In acute phase, the Th2 response is dominant in patients with CM. However, the immune response shifts towards to Th1 response in the stable phase, providing direct evidence that the imbalance of Th1-Th2 cytokines is related to the pathogenesis of CM.

doi: 10.3969/j.issn.1672-6731.2014.08.007