No abstract

SUMMARYThe role of antibody and cell-mediated immunity in the resistance of adult mice to intracutaneous infection with herpes simplex virus type I (HSV-x) was studied in nu/nu and nu/+ mice. In nu/+ mice, local skin lesions began to appear at the site of inoculation on the 4th day after intracutaneous challenge with the virulent Hayashida strain of HSV-I. Zosteriform skin lesions were observed in some animals. Almost complete regression of the lesions had occurred by the I6th day p.i. In contrast, all of the nu/nu mice that developed local skin lesions died after development of severe zosteriform skin lesions. After repeated intraperitoneal inoculations with the avirulent SKa strain of HSV-I, nu/nu mice did not produce detectable amounts of neutralizing antibody and succumbed to infection, indicating no development of resistance.Passively transferred neutralizing antibody prevented nu/nu mice from developing zosteriform skin lesions by the Hayashida strain of HSV-I, as long as the minimum concentration of serum antibody was maintained and prolonged their survival time. Adoptive transfer of I-o × lO 7 immune nu/+ spleen cells to nu/nu mice provided almost complete recovery from infection with production of sporadic low levels of anti-HSV antibody. The protective action of the immune spleen cells was lost after pre-treatment with anti-0 serum and fresh guinea pig serum prior to transfer of the cells. These data indicate that T cell-mediated cellular immunity plays a major role in recovery from intracutaneous HSV infection in mice, while antibody-mediated protection due to passive administration of HSV antibody is effective only in limiting the spread of virus.

The effects of endothelin-1 (ET-1) on intraocular pressure (IOP) and aqueous humor dynamics were studied in the rabbit eye. The intravitreal injection of 10(-5) M ET-1 (20 microliters) produced a biphasic IOP response consisting of an initial rise of 1 to 2 hours in duration, and a subsequent prolonged reduction lasting for more than 96 hours. Aqueous humor dynamics were determined 24 hours after the 10(-5) M ET-1 injection. Aqueous humor formation, measured fluorophotometrically, was decreased by 58%. Total outflow facility increased by 94%, according to measurement by two-level constant pressure perfusion. The change of uveoscleral outflow determined by fluorescein-dextran perfusion was not significant. The decrease in aqueous flow and the increase in total facility accounted for most of the IOP reduction after the ET-1 injection. Endothelin, which is endogenously present in the eye, may play a role in the regulation of intraocular pressure.

This study was performed to clarify the ocular hypotensive mechanism of topical isopropyl unoprostone (unoprostone), a novel prostaglandin (PG) metabolite-related drug, in the rabbit eye. The intraperitoneal administration of indomethacin (50 mg/kg) 1 hour before administration of topical 0.12% unoprostone partially diminished the intraocular pressure (IOP) reduction, and completely blocked the increase in aqueous PGE2 concentration caused by unoprostone. Aqueous humor dynamics measurements in the unoprostone- and the vehicle-treated contralateral eyes with indomethacin pretreatment revealed that aqueous flow determined by fluorophotometry was not significantly different, 2.3 +/- 0.3 and 2.4 +/- 0.2 microliters/min, respectively; the total outflow facility measurements determined by the two-level constant pressure perfusion method were 0.20 +/- 0.01 and 0.14 +/- 0.01 microliters/min/mmHg, respectively (p < 0.05); the uveoscleral outflow measurements determined by the fluorescein isothiocyanate-dextran perfusion method were 0.49 +/- 0.02 and 0.46 +/- 0.02 microliters/min, respectively (p < 0.05). The magnitude of the IOP reduction induced by unoprostone was estimated to be 5.2 mmHg, which agrees well with the actual IOP reduction. In conclusion, unoprostone lowers the IOP by affecting aqueous outflow pathways, primarily the pressure-dependent conventional pathway and the secondary uveoscleral outflow pathway in rabbits. Endogenous PGs induced by topical unoprostone are also involved in lowering the IOP in rabbits.

No abstract