Arachidonic acid metabolism to eicosanoids in herpes virus-infected rabbit cornea.

ABSTRACT

The metabolism of the polyunsaturated fatty acid, arachidonic acid (204, n-6) in rabbit cornea with varying severities of herpes simplex viral infection was investigated. The results indicate an active synthesis of the lipoxygenase and cyclooxygenase reaction products of arachidonic acid in central cornea and corneal-scleral rim. Stimulation of 12-hydroxyeicosatetraenoic acid (12-HETE) production in herpes-infected cornea was correlated positively with the severity of infection. Other eicosanoids were increased maximally in moderately infected corneas. The stimulation of eicosanoid synthesis was more evident in central cornea as compared to corneal-scleral rim. Herpes infection also caused a decline in the incorporation of radiolabeled arachidonic acid into membrane glycerolipids. These data indicate that the production of eicosanoids from arachidonic acid is stimulated in herpes-infected cornea. The stimulation may reflect the presence of phagocytic cells in the infected cornea, an enhanced capacity of the cornea itself to produce eicosanoids, or a combination of these effects. Decreased acylation of membrane lipids may be the result of infection-induced activation of fatty acid release mechanisms, which would lead to degradation of cell membranes. The presence of lipoxygenase reaction products in the herpes-infected cornea introduces a new factor for consideration in the design of therapeutic regimens for this disease.