Tissue Prostaglandin E2 Levels Research Articles

The immunosuppressive effects of a leukotriene B4 receptor antagonist on liver allotransplantation in rats.

The immunosuppressive effects of a leukotriene B4 (LTB4) receptor antagonist, ONO4057, on liver allotransplantation in rats were evaluated, and the levels of prostaglandin E2 (PGE2) in the liver tissue during rejection of the allografts examined. The rats were divided into four groups: group 1: Lewis rats (LEW) given a sham operation with dimethyl sulfoxide (DMSO); group 2: LEW given syngenic orthotopic liver transplantation (OLT) from LEW, with DMSO; group 3: LEW given allogenic OLT from ACI rats (ACI), with DMSO; and group 4: LEW given allogenic OLT from ACI, with ONO4057 as 10, 30, or 100 mg/kg per day dissolved in DMSO to subgroups 4a, 4b, and 4c, respectively. Histological examinations were performed, survival times monitored, and liver tissue PGE2 levels 3, 5, 7, and 14 days after transplantation measured. The mean graft survival times in groups 4a, b, and c, at 37.5 +/- 10.4, 52.2 +/- 24.4, and 34.0 +/- 4.9 days (mean +/- SEM), respectively, were significantly longer than that in group 3 (at 13.0 +/- 3.2 days). Moreover, the levels of tissue PGE2 in the liver allografts in group 4a were significantly higher than those in group 3 on days 5 and 7. These results suggest that ONO4057 has an immunosuppressive effect on liver allotransplantation since it reduces the activities of LTB4 which augments immune responses, and also because it indirectly increases the PGE2 level.

Prognostic significance of prostaglandin E2 production in fresh tissues of head and neck cancer patients.

Immunosuppressive prostaglandins may play a role in the biologic behavior of head and neck cancer. Increased levels of prostaglandin E2 (PGE2) have been measured in squamous cell carcinoma of the head and neck (SCCHN). To address this question, tissue levels of PGE2 were measured in tumor tissues, normal mucosa, and lymph nodes of 37 patients undergoing tumor resections. Tissue specimens were placed in culture media, and levels of PGE2 released into the supernatant were measured by radioimmunoassay. Tissue levels of PGE2 were significantly greater in tumor and normal mucosal tissues compared to lymph nodes (p = 0.0003). There was no difference between metastatic and tumor-free lymph nodes. Although tumor tissue levels of PGE2 were not associated with tumor stage, increased levels of PGE2 were associated with increased 2-year disease-free survival (p = 0.02). Although PGE2 may have adverse effects on local immune function in tumor tissues, improved survival of patients with increased local PGE2 production may be indicative of an enhanced immunologic response to the tumor which has a favorable impact on outcome.

Methylprednisolone does not decrease eicosanoid concentrations or edema in brain tissue or improve neurologic outcome after head trauma in rats.

Methylprednisolone was recently reported to significantly improve motor and sensory function after acute spinal cord injury in patients. Our study was designed to determine whether methylprednisolone exerts a beneficial effect after head injury. Diethyl ether-anesthetized rats were assigned to receive surgery with no cranial impact and no methylprednisolone (group A, n = 13); surgery with no cranial impact and intraperitoneal methylprednisolone (greater than or equal to 60 mg/kg) (group B, n = 8); surgery with cranial impact and no methylprednisolone (group C, n = 8, and group E, n = 8); or surgery with cranial impact and methylprednisolone (greater than or equal to 60 mg/kg) (group D, n = 15, and group F, n = 13). Neurologic severity score was determined at 1, 2, 4, and 24 h (when appropriate) after injury, and brain tissue eicosanoid levels and cerebral edema were determined when the animals were killed (4 h after injury in groups C and D and 24 h after injury in groups E and F). Treatment with methylprednisolone did not improve neurologic severity score or edema formation and did not alter brain tissue levels of prostaglandin E2, thromboxane B2, or 6-keto-prostaglandin F1 alpha at any time period. The authors conclude that methylprednisolone does not exert a beneficial effect on brain tissue edema or functional activity after cranial impact in rats.