Understanding the pro- & anti-inflammatory cytokine profile in Japanese encephalitis & their implications in survival outcome

Abstract

Background & objectives We aimed to conduct a comprehensive analysis of the cytokine profile in Japanese encephalitis (JE) patients and healthy individuals. Additionally, the correlation between the cytokines and the disease outcome in terms of survival or non-survival was also studied. Methods The study included 72 laboratory-confirmed JE cases and 50 healthy controls. Plasma levels of cytokines viz., GM-CSF, IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, and TNF-α were analysed using Bio-plex200 (Bio-Rad) following manufacturer's guidelines and compared between JE patients and healthy control group. Additionally, quantitative real-time PCR (qRT-PCR) was done for the quantification of expression of the above-mentioned cytokine genes. Results Except IL-4 and IL-13, the levels of GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-12, and TNF-α were significantly higher in JE patients in comparison to healthy controls. Significantly upregulated expression of IL-12, IL-10, and TNF-α was observed in the JE group as compared to that in healthy controls. Additionally, significantly downregulated expression of IL-4and IL-13 was observed in the JE group compared to the control group. Interpretation & conclusions A higher level of several pro-inflammatory cytokines and downregulation of a few anti-inflammatory cytokines were observed in JE patients compared to the healthy controls indicating co-association of inflammation with disease severity. Hence, a regulator of these pro and anti-inflammatory cytokines may stand out as a potential candidate for therapy in JE.

Keywords: Blood brain barrier; IL; Japanese encephalitis; TNF-α; cytokine; neuroinflammation.

Figure.

Comparative analysis of cytokine level in JE positive and healthy control samples. The plasma concentrations GM-CSF, IL-2, IL-5, IL-10, IL-12, IL-13, TNF-α, IFN-γ and IL-4 in JE and healthy control. Results are presented as mean±standard error of mean (SEM). JE vs. healthy control: P^***<0.001, ^****<0.0001.