Interleukin-1β exacerbates Eimeria tenella-induced cecal inflammation by disrupting intestinal barrier integrity and enhancing inflammatory mediator expression.

Eimeria tenella is a highly pathogenic protozoan parasite that causes severe hemorrhagic cecitis in chickens, leading to substantial economic losses to the global poultry industry. Interleukin-1β (IL-1β), a master regulator of inflammation, is strongly upregulated during E. tenella infection; however, its precise functional role in cecal inflammation remains unclear. In this study, recombinant chicken IL-1β and IL-6 proteins were expressed and purified using a prokaryotic expression system. Hyperimmune sera against IL-1β and IL-6 were generated in specific pathogen-free (SPF) chickens and administered passively to E. tenella-infected chickens. Clinical outcomes, cecal histopathology, ultrastructure using transmission electron microscopy, and expression of inflammatory mediators were evaluated. Neutralization of IL-1β or IL-6 significantly improved weight gain, reduced cecal lesion scores, and eliminated mortality in infected chickens. Ultrastructural analysis revealed that IL-1β neutralization preserved tight junction integrity and microvilli architecture in cecal epithelial cells. Mechanistically, IL-1β promoted inflammation by upregulating the expression of IL-6, IL-8, claudin-2, leukotriene D4 (LTD4), myeloperoxidase (MPO), and von Willebrand factor (vWF), while suppressing sealing tight junction proteins ZO‑1 and Occludin; neutralization of IL‑1β or IL‑6 significantly restored their expression. Combined neutralization of both IL-1β and IL-6 provided superior protection compared to single cytokine neutralization. These findings demonstrate that IL-1β plays a detrimental role in E. tenella-induced cecal inflammation by disrupting intestinal barrier integrity and amplifying inflammatory cascades, suggesting that targeting the IL-1β/IL-6 axis represents a potential therapeutic strategy for mitigating coccidiosis-induced pathology.