Anti-Inflammatory Effects of Lipoxin A4 in Salmonella Typhimurium-Induced Enteritis in Wenchang Chickens

<i>S. Typhimurium</i> infection has the capacity to elicit enteric inflammation and metabolic dysfunction among poultry. Prior research conducted by our laboratory observed an increase in LXA4 titers within the gut of Wenchang chickens following infection with <i>S. Typhimurium</i>. Based on this observation, the present study analyzed the changes in body weight, immune organ indices, the levels of intestinal inflammatory cytokines, as well as cyclooxygenase-2 (COX-2) expression in Wenchang chickens before and after infection. The findings indicated that <i>S. Typhimurium</i> infection led to reduced body weight and significantly decreased thymus and bursa indices. Furthermore, a significant elevation was observed in the transcript levels of pro-inflammatory mediators, including IL-1β, along with IL-6, and TNF-α, concurrently with an increase in the mRNA transcript levels of the enzyme COX-2. Treatment with LXA4 attenuated these alterations and effectively alleviated the inflammatory response. Additionally, an in vitro system was employed to validate the anti-inflammatory properties of LXA₄ against <i>S. Typhimurium</i>-induced inflammation in chicken HD11 macrophages. The results demonstrated that LXA4 attenuated the transcript levels of IL-1β, as well as IL-6, TNF-α, and COX-2, at various intervals (2, 12, and 24 h), thereby alleviating inflammation elicited by <i>S. Typhimurium</i> challenge. We employed the LXA4 receptor antagonist Boc-2 to explore the ALX/FPR2 signaling axis and noted the successful neutralization of LXA4-mediated anti-inflammatory properties by this antagonist in <i>S. Typhimurium</i>-challenged HD11 macrophages. Collectively, these findings indicate that <i>S. Typhimurium</i> triggers pro-inflammatory reactions across both in vivo chicken models and in vitro HD11 macrophage systems, whereas LXA4 effectively mitigates this inflammatory process. This research establishes the conceptual underpinnings necessary to advance the design of therapeutic modalities aimed at counteracting <i>S. Typhimurium</i> challenges within poultry populations.