The tumor necrosis factor α of the bony fish seabream exhibits the in vivo proinflammatory and proliferative activities of its mammalian counterparts, yet it functions in a species-specific manner

Information on the bioactivities of non-mammalian cytokines is scant due to the lack of the recombinant molecules and specific antibodies. We produced the mature predicted peptide of tumor necrosis factor α (TNFα) from the bony fish gilthead seabream (Sparus aurata L.) (sbTNFα), and its biological role was determined in vitro and in vivo. We first demonstrated by analytical size-exclusion chromatography that sbTNFα is an oligomeric protein but the dimer appears to predominate over the trimeric form, in contrast to mammalian TNFα. Intrapentoneal injection of native sbTNFα resulted in (i) priming of the respiratory burst of the peritoneal exudate and head-kidney (HK) leukocytes, the latter being the bone marrow equivalent in fish, (ii) rapid recruitment of phagocytic granulocytes to the injection site, and (iii) induction of granulopoiesis in the HK. Interestingly, sbTNFα was able to induce a strong proliferation of HK cells in vitro, whereas human TNFα did not. Conversely, sbTNFα was not cytotoxic for murine L929 fibroblasts.