Interleukin-6 (IL-6) is a multifunctional cytokine involved in innate and acquired immunity. In mammals, IL-6 can induce the secretion of acute-phase proteins (APPs) and antimicrobial peptides, activate macrophages and neutrophils, and regulate the expression of inflammatory cytokines in innate immunity, resulting in enhanced resistance to invading pathogens. In teleost fish, the functions of IL-6 are still unclear. In our previous studies using orange-spotted grouper (Epinephelus coioides) as an animal model, we demonstrated that IL-6 induces the Th2 pathway in acquired immunity and enhances antibody production. In the current study, we evaluated in greater detail the mechanisms underlying the functions of IL-6 in innate immunity. In gene expression assays, the expression of fish inflammatory cytokine genes (e.g., ifnγ, ccl4, il1β, tnfα 1, and tnfα 2), antimicrobial peptide genes (e.g., epinecidin 1, hepcidin 1, and hepcidin 2), and genes related to innate immunity (e.g., mx, crp, and complement C3) was higher in fish injected with recombinant IL-6 (rIL-6). The serum from those same fish also presented higher antibacterial activity and higher phagocytosis activity of leukocytes. In a pathogen challenge involving Vibrio campbellii and nervous necrosis virus, fish injected with rIL-6 presented a higher survival rate and lower pathogen count in the body. These results demonstrate that the administration of rIL-6 can activate innate immune responses and enhance resistance against invading bacterial or viral pathogens.

白细胞介素 6 (IL-6) 是一种参与先天性和获得性免疫的多功能细胞因子。在哺乳动物中，IL-6 可诱导急性期蛋白 (APPs) 和抗菌肽的分泌，激活巨噬细胞和中性粒细胞，并在先天免疫中调节炎性细胞因子的表达，从而增强对入侵病原体的抵抗力。在硬骨鱼中，IL-6 的功能仍不清楚。在我们之前的研究中使用橙斑石斑鱼（Epinephelus coioides) 作为动物模型，我们证明 IL-6 在获得性免疫中诱导 Th2 途径并增强抗体产生。在目前的研究中，我们更详细地评估了 IL-6 在先天免疫中的作用机制。在基因表达分析中，鱼类炎性细胞因子基因（如ifnγ、ccl4、il1β、tnfα 1和tnfα 2）、抗菌肽基因（如表内西丁 1、铁调素 1和铁调素 2）以及与先天免疫（如mx、crp和补体 C3) 在注射重组 IL-6 (rIL-6) 的鱼中更高。这些鱼的血清也表现出更高的抗菌活性和更高的白细胞吞噬活性。在涉及坎氏弧菌和神经坏死病毒的病原体挑战中，注射了 rIL-6 的鱼在体内表现出更高的存活率和更低的病原体数量。这些结果表明，rIL-6 的施用可以激活先天免疫反应并增强对入侵细菌或病毒病原体的抵抗力。