Interleukin-18 (IL-18) is a pro-inflammatory cytokine that belongs to the interleukin-1 (IL-1) family of cytokines. As occurs with IL-1β, it is synthetized as an inactive precursor peptide that is mainly processed by the cysteine protease caspase-1 in the inflammasome complex. In mammals, and in collaboration with IL-12, it has been described as an important cytokine controlling the Th1-mediated immune responses through the induction of IFN-γ. Although its function in mammals is well stablished, the activity of this cytokine in teleost remains to be elucidated. This could be due, among other things, to the absence of this gene in the fish model species zebrafish, but also to its complex regulation. As it was observed for rainbow trout and human, il18 splicing variants were also found in turbot, which could represent a regulatory mechanism of its bioactivity. In the case of turbot, three splicing variants were observed (SV1-3), and one of them showed an insertion of 10 amino acids in the middle of the potential caspase-1 cleavage position, reflecting that this is probably a form resistant to the processing by the inflammasome. Phylogenetic and three-dimensional analyses of turbot Il18 revealed that it is relatively well-conserved in vertebrates, although only a partial conservation of the gene synteny was observed between fish and mammals. As it was expected, turbot il18 splicing variants were mainly expressed in immune tissues under healthy conditions, and their expression was induced by a bacterial challenge, although certain inhibitions were observed after viral and parasitic infections. In the case of the viral challenge, il18 downregulations did not seem to be due to the effect of type I IFNs.

白细胞介素 18 (IL-18) 是一种促炎细胞因子，属于白细胞介素 1 (IL-1) 细胞因子家族。与 IL-1β 一样，它被合成为一种无活性的前体肽，主要由炎性体复合物中的半胱氨酸蛋白酶 caspase-1 加工。在哺乳动物中，它与 IL-12 合作，被描述为通过诱导 IFN-γ 控制 Th1 介导的免疫反应的重要细胞因子。尽管它在哺乳动物中的功能已得到很好的证实，但这种细胞因子在硬骨鱼中的活性仍有待阐明。除其他外，这可能是由于鱼类模型物种斑马鱼中缺乏该基因，也可能是由于其复杂的调控。正如在虹鳟鱼和人类身上观察到的那样，il18在大菱鲆中也发现了剪接变体，这可能代表了其生物活性的调节机制。在大菱鲆的情况下，观察到三个剪接变体（SV1-3），其中一个显示在潜在的 caspase-1 切割位置中间插入了 10 个氨基酸，这表明这可能是一种对由炎症小体处理。大菱鲆 Il18 的系统发育和三维分析表明，它在脊椎动物中相对保守，尽管在鱼类和哺乳动物之间仅观察到基因同线性的部分保守。正如所料，turbot il18剪接变体主要在健康条件下的免疫组织中表达，它们的表达是由细菌攻击诱导的，尽管在病毒和寄生虫感染后观察到某些抑制作用。在病毒攻击的情况下，il18下调似乎不是由于 I 型干扰素的影响。