先天免疫系統是魚類在疾病防治上非常重要的防線，魚類的先天免疫系統主要分成三大部分：物理屏障、體液成分與細胞成分，共同來抵抗各種水生病原菌的感染，使魚類維持在健康的狀態。介白素-6 (interleukin-6; IL-6) 屬於細胞激素 (cytokine) 中之淋巴球激素 (lymphokine)，主要誘導淋巴球的反應，在先天與後天免疫中扮演重要的角色。過去在哺乳類動物的研究，IL-6在先天性免疫可以誘導急性反應蛋白 (acute phase proteins; APPs) 和許多抗菌胜肽 (antimicrobial peptides; AMPs) 基因的表現，以及參與巨噬細胞與中性球的活化和調控其他炎症反應細胞激素的表現，以促進對細菌性疾病的抵抗能力；在後天免疫中可促使T cell和B cell分化，以及增進抗體產生的功能。在魚類中，IL-6的功能則仍有待一一證實。先前實驗室研究中，我們以點帶石斑魚 (Epinephelus coioides) 做例子，證實IL-6可以誘發在後天免疫系統中的Th2路徑反應，並促進抗體生成。在本研究中，我們進一步探討IL-6在先天性反應的可能機轉，並評估其在疾病抵抗上的效能。在目前的研究中，我們發現注射重組IL-6蛋白可調控各類炎症反應基因表現以及誘導抗菌胜肽基因的產生，同時可以影響其他的先天防禦機轉的表現，並進一步證實重組IL-6所誘導後的血清具有抗菌之能力，能夠有效的降低細菌數，在注射重組IL-6蛋白的狀況下，以Vibrio campbellii與Nervous Necrosis Virus攻毒，發現實驗組的存活率皆有顯著提升。由本研究的結果顯示石斑魚IL-6為一能誘導多種非特異免疫反應的因子，並且誘發這些免疫因子，有助於魚隻面對不論是細菌或病毒的侵襲。

Innate immune system is important for the disease resistance of fish. The innate immunity of fish is divided in three parts: physical barriers, humoral and cellular components, which are common to resistance variety water-pathogen infection and maintain the healthy statement of fish. Interleukin-6 (IL-6) is a cytokine of the lymphocytes hormone (lymphokine), mainly induce lymphocytes to reaction. It plays important roles in the innate and acquired immunity. In the research of mammalian, IL-6 can induce acute phase proteins (APPs) and antimicrobial peptide genes expression as well as stimulated the macrophage and neutrophil activation and regulate the inflammatory cytokines expression in the innate immunity, then enhance the resistance to bacterial disease. Regarding to the acquired immunity, IL-6 promotes T cell and B cell differentiation and increases the antibody production. In teleost fish, the functions of IL-6 are not confirmed yet. Previous studies in our laboratory use Epinephelus coioides to be the animal model, confirmed that IL-6 induce the Th2 pathway in the acquired immunity and enhance antibody production. In my study, investigate the mechanism of IL-6 in innate immunity and evaluate its efficacy of disease resistance. In the current study, inject of recombinant IL-6 (rIL-6) regulate some inflammatory cytokine, antimicrobial peptide and other innate immunity related genes. Further, we comfirm the antibacterial activity in serum by rIL-6 induction, can reduced the bacterial number in the in vitro test, and enhance the phagocytosis of head kidney leukocytes. Finally, in the in vitro challenge test, fish injection of rIL-6 was highersurviver while charllenged by Vibrio campbellii and Nervous Necrosis Virus, and reduced the pathogen. In summary, grouper IL-6 was a molecular that could induce multiple innate immune reactions, which will help to resistant the pathogen invasion.

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