Causal Relationship Between Inflammatory Cytokines and Pancreatitis Risk

Abstract

The causal relationship between inflammatory factors and acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced acute pancreatitis (AAP), and alcohol-induced chronic pancreatitis (ACP) remains unclear. We aimed to examine the casual relationship between inflammatory factors and various forms of pancreatitis, namely, AP, CP, AAP, and ACP. We employed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between 91 inflammatory factors and 41 inflammatory factors with respect to pancreatitis. The primary analysis involved the use of the inverse variance weighting (IVW). MR-Egger intercept test, Cochran's Q test, MR-PRESSO test, and Leave-One-Out analysis were used to assess the robustness of our findings. IVW analysis revealed evidence of association between 24 inflammatory cytokines and pancreatitis. Specifically, six cytokines were associated with AP, eight cytokines were associated with CP, three cytokines were associated with AAP, and seven cytokines were associated with ACP. The most significant associations were observed with β nerve growth factor (odds ratio [95% confidence interval]: 6.05 [1.59, 23.01]) and interleukin-4 [IL-4; 2.56 (0.91, 7.16)] in AAP, as well as interleukin-2 receiver subunit beta and IL-4 in ACP. Our findings suggest that certain inflammatory cytokines may have a significant role in the development of pancreatitis.

Keywords: GWAS; Mendelian randomization; SNPs; inflammatory cytokines; pancreatitis.

FIG. 1.

Causal correlations of cytokines on pancreatitis (AP, CP, AAP, and ACP). The change in the odds ratio (OR) of 4 pancreatitis per 1-SD rise in the cytokine level is shown by OR and 95% confidence interval. AAP, alcohol-induced acute pancreatitis; ACP, alcohol-induced chronic pancreatitis; AP, acute pancreatitis; CP, chronic pancreatitis; SD, standard deviation.