Fish & Shellfish Immunology (1995) 5, 549-567 Eicosanoids and their role in immune modulation in fish--a brief overview ANDREW F. ROWLEY*, JOHN KNIGHT, PAUL LLOYD-EVANS,JASON W. HOLLANDAND PHILIP J. VICKERS'~ School of Biological Sciences, University of Wales, Swansea, Singleton Park, Swansea, SA2 8PP, U.K., and tMerck Frosst Centre for Therapeutic Research, Pointe-Claire-Dorval, Quebec, Canada Eicosanoids have been demonstrated to play a central role in immune regulation in mammals brought about by their direct effects on cells such as macrophages and lymphocytes or by their indirect effects via cytokines. Studies have shown that fish mononuclear phagocytes, granulocytes and thrombocytes synthesize and release both cyclooxygenase- and lipoxygenase- derived products such as prostaglandin E._,, leukotriene B~ I and lipoxin A 4. Whether lymphocytes have the ability to generate leukotrienes and lipoxins is still unclear but they do appear to have 12-1ipoxygenase activity that leads to the generation of 12-hydroxy fatty acid derivatives. As in mammals, leuko- triene and lipoxin biosynthesis requires the presence of a 5-1ipoxygenase activating protein-like molecule that is sensitive to the action of the specific inhibitor, MK-886. The prostaglandin-generating ability of trout macrophages can be altered by incubation with lipopolysaccharide suggesting the possible presence of an inducible cyclooxygenase activity. Prostaglandins have been found to suppress the mitogen-induced proliferation of trout leucocytes and the generation of humoral antibody and plasma cells both in vivo and in vitro. The lipoxygenase products, leukotriene B,I and lipoxin A 4, have more variable effects ranging from inhibition to stimulation depending on the assay system employed. Overall, there is clear evidence that eicosanoids play a role in immune regulation in fish in a similar way to that reported in mammals. i: 1995 Academic Press Limited Key words: Eicosanoid, lipoxygenase, cyclooxygenase, 5-1ipoxygenase activating protein, prostaglandins, leukotrienes, lipoxins, leuco- cytes, macrophages, lymphocytes, immune regulation, fish, rainbow trout. I. Introduction One of the hallmarks of the mammalian immune system is the exquisite array of regulatory mechanisms that integrate the cellular activities operating in this homeostatic response to foreign invaders or altered 'self'. The interplay between cytokines, eicosanoids and various leucocyte types well exemplifies the complexity of this system. Not only can cytokines, such as interleukin-1 (IL-1), induce prostaglandin E,_, (PGE2; a type of eicosanoid) generation from *To whom all correspondence should be addressed. ¶IPresent address: Department of Molecular Sciences, Pfizer Central Research, Sandwich, Kent, CT139NJ. 549 1050 4648/95/080549+19 $12.00/0 c 1995 Academic Press Limited