In vitro study of wood creosote activity against anisakid larva-derived proteins: implications for anisakis food allergy

In countries where raw fish are consumed, anisakid larvae Infection is a public health concern, and Japan remains among the highest-incidence countries. Besides gastrointestinal symptoms caused by larval invasion of the gastric and intestinal mucosa, anisakid infection can elicit severe allergic reactions even when larvae are nonviable, and no specific therapy for the allergic manifestation has been established. Wood creosote (WC), a wood-tar distillate containing phenolic compounds, has been reported to inhibit anisakid larval motility. Here, we examined whether WC modulates epithelial responses to anisakid larvae proteins. A crude extract prepared from untreated anisakid larvae (CE) was applied to Caco-2 cells and induced epithelial activation, including increased expression of IL-6 and IL-8, as well as increased paracellular permeability assessed by Lucifer Yellow (LY) flux. To assess the impact of WC, anisakid larvae were treated with WC prior to preparation of a crude extract (CEWC). Compared with CE, CEWC significantly reduced LY flux (p < 0.05) and attenuated cytokine responses associated with allergic inflammation. IL-6 and IL-8 expression decreased by 61% and 30%, respectively, and mRNA analyses confirmed significantly lower IL-6 and IL-8 levels in cells exposed to CEWC than in those exposed to CE (p < 0.05). These results indicate that WC attenuates anisakid antigen–driven epithelial activation in vitro. WC may therefore reduce the allergenic potential of anisakis larval proteins, warranting further investigation as a candidate approach for managing anisakid larvae-associated allergy.