Causal relationship between circulating inflammatory proteins and risk of different types of encephalitis: A two-sample Mendelian randomization study

Abstract

Background: Cytokines are potent molecules of the immune response. They act at the site of inflammation and circulate in the bloodstream. However, there are few studies on encephalitis and circulating inflammatory proteins.

Methods: In this study, Mendelian randomization (MR) was used to explore the potential causal effect of 91 circulating inflammatory proteins on 3 different types of encephalitis. Causal effects were examined using Steiger, MR-Egger, weighted median, and inverse variance weighting (IVW) methods. IVW methods were primarily used for results interpretation. In addition, sensitivity analyses were performed, including assessment of heterogeneity, horizontal pleiotropy, and Leave-one-out techniques.

Results: We subjected 91 circulating inflammatory proteins to MR analysis of causality with each of the three types of encephalitis. The results suggested that the inflammatory factors with a potential causal relationship with viral encephalitis were caspase 8, C-X-C motif chemokine 6, interleukin-10, interleukin-15 receptor subunit alpha, interleukin-7, and TNF-beta. Inflammatory factors potentially causally associated with acute disseminated encephalomyelitis are beta-nerve growth factor, cystatin D, interleukin-7, Latency-associated peptide transforming growth factor beta 1,and neurotrophin-3.Inflammatory factors potentially causally associated with autoimmune encephalitis are C-C motif chemokine 25, hepatocyte growth factor, latency-associated peptide transforming growth factor beta 1, programmed cell death 1 ligand 1, sulfotransferase 1A1, and tumor necrosis factor.

Conclusion: This finding identifies potential causal effects of certain circulating inflammatory factors on susceptibility to three types of encephalitis. It also suggests the therapeutic potential of modulating the levels of these cytokines. A basis for further research is provided.

Keywords: Acute disseminated encephalomyelitis; Autoimmune encephalitis; Circulating inflammatory proteins; Mendelian randomization; Viral encephalitis.