The Influence of Cortisone on Experimental Viral Infection

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As a host-produced protective substance formed in response to laboratory infections with many viruses, interferon has received deserved attention as a possibly important determinant of the outcome of viral infections in nature. Indeed, recent reports have demonstrated the presence of interferon in blood (1), cerebrospinal fluid (2), pharyngeal washings (3), and dermal crusts (4) during the course of infection in man. Evidence is contradictory, however, as to whether the synthesis of interferon occurs simply as a consequence of viral infection that happens to coincide with the termination of viral replication, or whether its formation is the cardinal factor in bringing this termination about. In the intact animal host this question is difficult to resolve, especially since the formation of specific and nonspecific immune substances also occurs coincident with recovery from viral infection.Viral infection of the chick embryo lacks the simplicity of in vitro infection of cell or tissue culture, but comprises an in vivo system less complex than the infected animal. 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.The present paper reports studies of the pathogenesis of infection with three

Section: The Influence Of Hydrocortisone On the Course Of Infection Wsupporting

confidence: 81%

The Influence of Cortisone on Experimental Viral Infection

Smart

Kilbourne

1966

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“…(a) Ribonudease, which inhibits the synthesis of influenza viruses in the egg (14) (as does cortisone (1,15)), has been found in this laboratory not to inhibit interference.…”

Section: The Mechanism By Which C-z1 Steroids Fnduce Negation Of Viramentioning

confidence: 87%

“…The demonstration that cortisone inhibits viral interference in the case of influenza B provides an explanation for the late increase in virus observed with active inocula (1). Evidence has been presented that the dynamics of Lee virus increase in ovo are altered and the incremental rate is reduced when a critical yield of 20 particles/cell has been effected, regardless of the number of infective particles inoculated (24).…”

Section: Discussionmentioning

confidence: 99%

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The Influence of Cortisone on Experimental Viral Infection

1957

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The interference with viral synthesis which is induced by large quantities of non-infective influenza B virus is inhibited or negated with small quantities of cortisone and other C-21 steroids. The specificity of this effect is attested by the inactivity of 11-alpha hydroxy epimers of highly active compounds. Maximal activity in negation of interference is associated with the presence of oxygen at the C-11 position of the steroid molecule. In view of the demonstration that negation of interference can occur, it is concluded that the phenomenon of multiplicity reactivation of non-infective virus is not primarily influenced by cortisone. Rather, it is suggested that the reactivation phenomenon is unmasked by cortisone through its inhibiting effect on the autointerference intrinsic in multiplicity infection. If it is accepted that influenza virus infections in ovo are self-limited in part by viral autointerference, present evidence is consistent with the view that negation of this autointerference is the mechanism by which cortisone induces definitively increased yields of virus.

“…It has also been demonstrated that changes in the dis-tribution ratios of allantoic fluid and CAM virus are affected by cortisone only as the secondary result of reduction in viral synthesis (7). With studies of the kinetics of interferon formation in prospect, it was essential to determine whether measurement of allantoic fluid interferon would be representative of tissue concentrations at various time intervals in both cortisone-injected and control embryos.…”

Section: Kinetic Studies Of Interferon Increase--parallelism Of Cell-mentioning

confidence: 99%

The Influence of Cortisone on Experimental Viral Infection

Smart

Kilbourne

1966

Self Cite

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.