Abstract

The systemic and local inflammatory response in patients after surgical operation is closely related to the quality of the wound healing. Low-quality wound healing and defects in the suture technique lead to the occurrence of incisional hernia (IH). However, the causal relationship between human circulating inflammatory cytokines, immune cell traits, and the risk of IH remains unclear. We used summary data from genome-wide association studies to assess the causal relationship between 91 types of circulating inflammatory factors, 731 types of circulating immune cell traits, and the risk of IH. The outcome dataset was obtained from FinnGen, including 6,336 patients with IH and 232,612 controls. We performed Mendelian Randomization (MR) analysis to identify their causal relationship and immune cell phenotypes upstream of inflammatory factors. Inverse variance weighting is considered to be the main analysis method. Among the identified cytokines, TNF-related activation-induced cytokine levels were associated with a lower risk of IH (OR: 0.89; 95% CI: 0.82-0.96; P = 0.003). In contrast, interleukin-5 levels were associated with an increased risk of IH (OR: 1.18; 95% CI: 1.06-1.31; P = 0.003). Additionally, a significant causal relationship was found between four immune cell traits and the risk of IH (P < 0.01). Through two-step MR analysis, we determined that interleukin-5 levels mediate the causal relationship between the relative count of CD25hi % CD4 + in Treg cells and the higher risk of IH. This study found a causal relationship between specific inflammatory cytokines, immune cell traits, and risk of IH. These results can help surgeons predict the risk of IH and take preventive measures.

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