The Influence of Cortisone on Experimental Viral Infection

Abstract

The initial observations that cortisone may act as an inhibitor of viral interference (11, 4) are now explicable as an inhibitory effect on interferon synthesis. The suggestion that the action of interferon is also inhibited by cortisone or its analogues (6) has not been confirmed in a plaque reduction type of interferon assay system in which autointerference by the challenge inoculum is a lesser problem. In this respect, the present results are in accord with those obtained by DeMaeyer and DeMaeyer (8) with hydrocortisone in a system in which a low multiplicity (0.1) Sindbis virus infection in monolayer culture was employed with cytopathic effect (CPE) as an end-point. It has been shown that hydrocortisone is restrictive to the synthesis of interferon induced by inoculation of either infective or inactivated virus into the chick embryo, and that this inhibitory effect is temporary. However, in another study in the chick embryo, three spaced injections of hydrocortisone (0.25 mg/dose) prevented the appearance of detectable interferon during the entire 64 hr observation period following inoculation of 103.3 EID50 of Lee virus (12). The importance of explicit definition of experimental conditions in assessing hormonal effects on infection is illustrated by the capacity of hydrocortisone either to inhibit or increase interferon synthesis in vitro, depending on the proportion of inactivated and infective virus in the inoculum employed, and the time at which interferon is measured. As suggested previously, it is not unlikely that similar shifts in hormone-virus-interferon balance may operate in vivo to influence the outcome of infection.

The Influence of Cortisone on Experimental Viral Infection

“…The experimental procedures were identical with those described in a previous communication on this study (5) with the following additions. …”

“…Thus the interval between the estimated (interpolated) initial appearance of measurable HA and of interferon in allantoic fluid was only 15 hr for Lee infection, 24 hr for Mel., and 36 hr in the case of PR8. These differing intervals represent real differences in the rates of interferon synthesis because earlier experiments had shown that allantoic fluid interferon activity paralleled closely that of chorioallantoic membrane---the site of viral and interferon synthesis (5). As these earlier experiments had been done principally with Lee virus, interferon activity was searched for in CAM from PR8-infected eggs during the first 48 hr of infection, but was not found.…”

“…The advantages of this system have been cited (5) and it lends itself well to the study of the pathogenesis of viral infection divorced from the complicating effects of specific antibody formation oc temperature response. Also, in the case of influenza virus infection of the cells lining the allantoic sac, cellular destruction and inflammatory response may be quanfitated in parallel with virus and interferon formation in assessing the severity or virulence of infection.…”