The role of the Inflammatory Cytokine Interleukin-6 (IL-6) in moderating the relationship between pesticide exposure and metabolic syndrome in vegetable farmers
Pesticide exposure has been associated with metabolic syndrome (MetS). However, the moderating role of inflammatory cytokines, such as interleukin-6 (IL-6), remains unclear. This study examined how IL-6 moderates the relationship between acetylcholinesterase (AChE) activity, as a pesticide-exposure biomarker, and the risk of MetS among vegetable farmers. We conducted a case–control study involving 134 male farmers (44 MetS cases and 90 controls) selected from a 13-week population screening of 307 farmers in Kuningan, West Java from January to May 2025. Exposure was assessed through the measurement of acetylcholinesterase (AChE) activity, while IL-6 served as an inflammatory biomarker. MetS was diagnosed according to the International Diabetes Federation criteria. Venous blood samples were collected twice for AChE analysis and once for IL-6 measurement. Moderation analysis using linear regression with the PROCESS Macro SPSS revealed that IL-6 significantly moderated the effect of AChE on waist circumference (WC), systolic and diastolic blood pressure (BP), and MetS. The conditional effect of AChE on MetS according to IL-6 values increased with high inflammation (B = 0.0031, p = 0.0004 for WC; B = 0.0059, p = 0.0008 for systolic BP; B = 0.0027, p = 0.0064 for diastolic BP; and B =-0.0009, p = 0.0041 for MetS). Scatter plot patterns further supported the biological plausibility of this moderating mechanism. IL-6 modifies the strength and direction of the inflammatory response, enhancing the impact of pesticide exposure on key MetS components. These results underscore the central role of IL-6 in the cholinergic pathway and indicate that lowering chronic low-dose pesticide exposure may reduce inflammation-related metabolic risks.