Chained mediation of interleukins linking fluoride exposure to frailty: a cohort study of skeletal fluorosis patients in China

Frailty prevalence (5.9%) surpassed that of the general population (2.3%). A high uF value was directly associated with frailty risk (β = 0.2856, P < 0.001). Two potential pathways were identified: the inflammatory cascade: uF→IL-6↑ (β= 0.2947) → IL-1β↑ (β= 0.3936) →frailty (β= 0.0893), and the indirect association accounted for 3.6% of the total effect. Muscle-nutrition depletion: IL-1β↑ → sarcopenia↑ (β= 0.1137)→ increased undernutrition risk↑ (β=-0.2148)→ frailty (β=-0.1990); the indirect association accounted for 4.2% of the total effect. IFN-α attenuated the association of fluoride with IL-1β (P = 0.0113) and was linked to lower frailty risk (β = -0.086, P < 0.01). CONCLUSIONS : The"IL-6→IL-1β" pathway is a potential mechanism for inflammation-related frailty, and nutritional interventions could disrupt the "IL-1β→sarcopenia→malnutrition" cycle. IFN-α has a protective effect on fluoride-induced inflammation.