Immunoregulatory activities of eicosanoids in the rainbow trout (Oncorhynchus mykiss).

Eicosanoids such as prostaglandins (PG), leukotrienes (LT) and lipoxins (LX) have been shown to be potent immunoregulatory molecules in mammals. To determine if they have similar roles in 'lower' animals, rainbow trout (Oncorhynchus mykiss) were immunized with either sheep erythrocytes or Aeromonas salmonicida in the presence or absence of the stable analogue of PGE2, 16,16-dimethyl-PGE2, and the number of plaque-forming cells (PFC) or specific antibody levels determined. The higher dose of 16,16-dimethyl-PGE2 (200 micrograms/kg body weight) caused a significant reduction in both PFC number and antibody titre compared with the control. The effect of PGE2, PGE3, 16,16-dimethyl-PGE2, LTB4, LTB5, LXA4, 12-HETE and 12-HEPE on PFC generation following the in vitro challenge of trout splenocytes with sheep erythrocytes was also determined. All of the prostaglandins tested showed a dose-dependent inhibition of PFC after 11 days in culture, while of the remaining eicosanoids only LXA4 had any effect on PFC number, with a dose-dependent stimulatory effect. The cyclo-oxygenase inhibitor, indomethacin, also caused a stimulation in the number of PFC generated, with a maximal effect at c. 25 microM, while the lipooxygenase inhibitors, esculetin and nordihydroguaiaretic acid (5-100 microM), had no significant effect on PFC generation at all concentrations tested. The present results show that, as in mammals, prostaglandins and the cyclo-oxygenase pathway are also important in the regulation of the piscine humoral immune response. Of the lipoxygenase products tested, however, only LXA4 had any significant effect on PFC generation, suggesting that these compounds have only a limited role to play in immune regulation in this organism. Overall this work shows that eicosanoids have a long evolutionary history in immunoregulation, probably dating back at least to the appearance of bony fish some 400 million years ago.