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SummaryEvidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet “exhaustion”.

Evidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet "exhaustion".

Some studies suggest that leukocytic pyrogen (LP) increase hypothalamic prostaglandins which, in turn, affect hypothalamic thermoregulatory neurons to produce fever. The present study used radioimmunoassays to quantitate the ability of guinea pig hypothalamic tissue slices to produce prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2). Dose- and time-dependent prostaglandin increases occurred when these slices were perfused with LP media. Steady-state levels of tissue release were reached at 0-3 min for 6-keto-PGF1 alpha, at 6-9 min for PGE2 and PGF2 alpha, and at 12-15 min for TxB2. With the exception of 6-keto-PGF1 alpha, all substances showed continuous dose-response relationships for concentrations ranging from 0.001 to 0.25 LP dilutions. Tissue PGE2, for example, was 0.7 pg X min-1 X mg-1 with the 0.001 LP dilution and 8.7 pg X min-1 X mg-1 with the 0.25 LP dilution. Indomethacin blocked much of the LP-induced prostaglandin increase. Although there is a relationship between hypothalamic LP and prostaglandins in response to physiological LP levels, tissue prostaglandins are several orders of magnitude lower than concentrations necessary to produce fever by hypothalamic microinjection. This suggests that prostanoids, such as PGE2, may not be the sole mediators of fever induced by leukocytic pyrogen.

These studies evaluated further the relationship between the metabolism of reactive oxygen species (ROS) and prostaglandins in human granulocytes. Our experiments examined (1) the effects of several scavengers of ROS on thromboxane B2 (TXB2) production by zymosan-stimulated PMNs, (2) the capacity of the granulocytes of patients with chronic granulomatous disease (CGD) to produce TXB2, and finally (3) the generation of oxygen radicals in PMNs stimulated to produce TXB2 by the enzyme phospholipase A2. Our results confirm that both zymosan- and PMA-stimulated PMNs release increased amounts of TXB2. This enhanced production of TXB2 by normal PMNs could not be impaired and, in fact, appeared to be enhanced by scavengers of ROS. The PMNs of one patient with CGD produced TXB2 in an amount similar to those of healthy persons, whereas the TXB2 produced by the PMNs of a second patient was markedly increased. Finally, the enzyme phospholipase A2 stimulated TXB2 production in PMNs without stimulating the production of ROS. These data indicate that the activation of prostaglandin metabolism in PMNs is not dependent on the simultaneous production of ROS by these cells. However, the simultaneous production of ROS may be associated with an alteration of prostaglandin metabolism.