Methylprednisolone on circulating eicosanoids and vasomotor tone after endotoxin

Area of Science:

• Pharmacology
• Physiology
• Biochemistry

Background:

• Endotoxin induces acute pulmonary and systemic vasomotor changes.
• Eicosanoids, like thromboxane and prostacyclin, mediate these endotoxin effects.
• Steroids, in vitro, inhibit phospholipase A2, potentially reducing eicosanoid production.

Purpose of the Study:

• To investigate if high-dose methylprednisolone prevents endotoxin-induced eicosanoid production and vasomotor changes in dogs.
• To determine the in vivo effect of methylprednisolone on endotoxin-mediated eicosanoid release and hemodynamic alterations.

Main Methods:

• Dogs were administered methylprednisolone (40 mg/kg) at different times relative to endotoxin (150 µg/kg).
• Levels of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1α) were measured using radioimmunoassay.
• Systemic blood pressure and systemic vascular resistance were monitored.

Main Results:

• Methylprednisolone alone did not affect circulating eicosanoids.
• Pre-administration of methylprednisolone (2.5h before endotoxin) increased 6-keto-PGF1α levels (P<0.05) and did not inhibit TxB2.
• Immediate methylprednisolone administration enhanced both TxB2 and 6-keto-PGF1α levels (P<0.05).
• Indomethacin counteracted steroid-enhanced 6-keto-PGF1α and the fall in blood pressure/vascular resistance.

Conclusions:

• High-dose methylprednisolone in vivo does not prevent endotoxin-induced eicosanoid production.
• Steroids actually increased circulating levels of TxB2 and 6-keto-PGF1α, contributing to vasodilation.
• Steroids exert a complex, potentially vasodilatory, effect in endotoxemia, beyond eicosanoid modulation.