Anti-inflammatory actions of enprofylline, a modified xanthine, in the canine forelimb

It has been previously reported that enprofylline (3-propyl xanthine) prevents histamine-mediated edema formation in the guinea pig lung. To further assess the potential anti-inflammatory effects of enprofylline, we infused it intra-arterially into the canine forelimb before and during a local intra-arterial infusion of histamine (4 micrograms/min) while monitoring forelimb skin lymph parameters. Infusion of enprofylline at 2 mg/min significantly decreased forelimb arterial pressures and increased heart rate and pulse pressure. Subsequent infusion of histamine caused a further reduction in forelimb arterial pressures and an increase in lymph flow, protein concentration, and protein transport similar to that seen with the infusion of histamine alone. Infusion of enprofylline at 5 mg/min decreased forelimb arterial pressures and systemic pressure. Subsequent histamine infusion further reduced forelimb arterial pressures, but the increase in lymph parameters was markedly attenuated. Enprofylline infused at 10 mg/min also decreased forelimb arterial and systemic pressures, but subsequent histamine infusion was essentially without effect on lymph parameters. To assess the role of catecholamines in enprofylline-mediated attenuation of histamine edema formation, we infused enprofylline at 5 mg/min in the presence of a beta 2-receptor blockade produced by the intra-arterial infusion of ICI 118551. The effects of enprofylline and histamine on vascular pressures were similar to those seen in the absence of beta 2-receptor blockade, but lymph flow, protein concentration, and protein transport increased similar to that seen with histamine alone. These data indicate that enprofylline is capable of attenuating histamine-induced increases in microvascular permeability, but this action of enprofylline is of an indirect nature, mediated through the release of catecholamines.