The eicosanoids are a family of lipid-derived autocoids that are released in response to a variety of physical and hormonal stimuli. In this study, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured in the digital veins of clinically normal horses and horses with chronic laminitis to determine whether these arachidonic acid metabolites have a role in mediating signs of hoof pain and lesions associated with chronic laminitis. Horses were evaluated at rest and after a brief exercise period, to determine whether eicosanoids are released into the circulation after mild concussion. Digital vein eicosanoid concentrations in horses with signs of hoof pain attributable to chronic laminitis were not different than those in clinically normal horses. There was no difference in resting and postexercise PGE2 or LTB4 concentrations. Mean digital vein PGE2 concentration for the 2 groups was 187.18 pg/ml, whereas mean digital vein LTB4 concentration for the 2 groups was 74.71 pg/ml. These data do not support the hypothesis that PGE2 and LTB4 have a role in mediating the signs of pain and pathologic features of chronic laminitis.

Two experiments were performed to study the relationship between leukotriene B4 (LTB4) synthesis and placental separation and uterine involution in the cow. In experiment I, the concentration and synthesis of LTB4 by caruncular tissue was lower in cows with retained fetal membranes (RFM cows, n = 11) than in cows that expelled the fetal membranes normally (NFM cows, n = 19). The presence of bacterial cell wall, especially of alpha-hemolytic streptococci and coagulase positive staphylococci enhanced LTB4 synthesis by allantochorion only in NFM cows. In the RFM group, Escherichia coli lipopolysaccharide decreased allantochorionic LTB4 synthesis. With caruncle, only epidermal growth factor increased LTB4 production in NFM cows. In experiment II, the caruncular and endometrial secretion of LTB4 was lower in cows with subuterine involution (SUI cows, n = 5) or cows with SUI and RFM (SUI+RFM cows, n = 4) than in cows with normal uterine involution (NUI cows, n = 8). This decrease was especially noticeable in the previously gravid horn. In the three uterine involution groups, there were no differences in LTB4 synthesis by caruncular tissue taken from the previously gravid horn. However, progesterone and a bacterial suspension of E. coli reduced the synthesis of LTB4. Estradiol had no effect on LTB4 synthesis at the end of the postpartum period. These results suggest that LTB4 may play an important role in both placental separation and uterine involution in cattle and LTB4 synthesis may be modulated by endocrine and bacterial factors.

In each of 5 groups of dogs, 0.05 ml of 1 of the following solutions was injected into the anterior chamber of both eyes: phosphate-buffered saline solution, 0.001 microg of prostaglandin F2 alpha (PGF2 alpha), 0.01 microg of PGF2 alpha, 0.1 microg of leukotriene D4 (LTD4), and 1 microg of LTD4. A 10% solution of sodium fluorescein was injected IV (14 mg/kg of body weight) at the same time, and pupil size, intraocular pressure, and anterior chamber fluorescence were measured for 1 hour after injections. In a dose-dependent manner, Pgf2 alpha was a potent miotic. A significant effect on intraocular pressure was not detected when the groups given PGF2 alpha were compared with the control group. When compared with LTD4, PGF2 alpha Significantly (P < 0.05) increased the breakdown of the blood-aqueous barrier, as evidenced by increased fluorescein leakage into the anterior chamber. Leukotriene D4 caused a decrease in pupil size only at 5 minutes, compared with that of the control group. Intraocular pressure was greater (but not significantly) in the group given 1 microg of LTD4.

The lipoxygenase metabolites of arachidonic acid have an important role in lymphocyte activation. We used a specific 5-lipoxygenase inhibitor, A-63162, to examine the role of 5-lipoxygenase (5-LO) in equine blood mononuclear cell (BMC) proliferation and leukotriene B4 (LTB4) synthesis after stimulation with mitogen (phytohemagglutinin, PHA) or calcium ionophore (A23187). The A-63162 inhibited PHA-induced equine BMC proliferation and, at the same concentration, also inhibited A23187-induced LTB4 synthesis. The presence of exogenous interleukin 2 (IL-2) or the cyclooxygenase inhibitor indomethacin, failed to reverse the immunosuppression caused by A-63162. Further, we found that A-63162, at the concentration that inhibited BMC proliferation and LTB4 synthesis, had no effect on BMC viability. The addition of the specific protein kinase C inhibitor, H-7, did not inhibit A23187-induced LTB4 synthesis. Results indicate that 5-lipoxygenase metabolites may have an important role in equine lymphocyte activation and that protein kinase C has no role in regulating LTB4 production after A23187 stimulation.