Bioactivity of orange-spotted grouper (Epinephelus coioides) interleukin-6 in innate immunity: Inducing inflammation, antimicrobial peptides, and innate immune molecular gene expression as well as activating phagocytosis of leukocytes and increasing survival under Vibrio and NNV infection

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.