Toxic effect of carbon monoxide and 41 inflammatory cytokines: A bidirectional 2-sample Mendelian randomization study

一氧化碳和41种炎症细胞因子的毒性作用:一项双向双样本孟德尔随机化研究

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Abstract

Carbon monoxide (CO) poisoning causes an important public health problem, tens of thousands of deaths reported on a global scale each year. Previous research has identified various inflammatory cytokines as key players in the inflammatory response associated with CO poisoning. Mendelian randomization (MR) was utilized to rate the causation between CO poisoning and 41 inflammatory cytokines. Our research applied the MR method to analyze the data from 41 inflammatory cytokines in 8293 Finnish individuals, alongside the toxic effect of CO in a genome-wide association study summary containing 2,17,123 individuals. The inverse-variance weighting approach was adopted for the bidirectional MR analysis to explore these relationships, supplemented by multiple MR methods to ensure robustness. Two analytical methods were utilized to assess the assumptions, including the MR-Egger intercept test and the MR-PRESSO test. Our results of the 2-sample MR analysis revealed that IL-10, IL-1β and IL-13 had causal effects on CO toxicity (IL-10: β: 0.52; 95% CI: 0.02, 1.03; P = 4.19E-02; IL-1β: β: -1.23; 95% CI: -2.27, -0.20; P = 1.91E-02; IL-13: β: 0.54; 95% CI: 0.24, 0.85; P = 4.77E-04), while CO toxicity showed no significant causal effect on any of the 41 inflammatory cytokines. Our study suggests that IL-10, IL-1β, and IL-13 may be important players in immune response regulation, impacting CO poisoning prognosis. Our research offers fresh perspectives on the disease mechanisms underlying CO poisoning and pinpoints potential therapeutic targets for intervention.

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