Interferon induction with statolon in the intact animal.

Kleinschmidt, W. J.; Murphy, E B

doi:10.1128/mmbr.31.2.132-137.1967

Cited by 15 publications

(16 citation statements)

References 12 publications

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“…Duration of activity. The duration of activity observed with statolon (administered intraperitoneally) against MM virus was 30 days (11). Preliminary experiments with statolon (IN) against influenza virus (IN) indicated shortened persistence in activity over that seen against MM virus, and experiments of shorter periods were then conducted.…”

Section: Resultsmentioning

confidence: 99%

“…The persistence of the protective effect of intranasally instilled statolon in mice is sufficiently prolonged to make statolon a candidate for similar testing to determine its efficacy via the extranasal route in man. Hyporeactivity seen with statolon lasting about five days (11), during which time further interferon formation is switched off, would not pose a problem, for the duration of activity exceeds this period. Hill et al (5) have observed protection in mice against influenza virus with IN administered poly inosinic acid :poly cytidylic acid (poly I:C), the synthetic DS-RNA molecule, a potent inducer of interferon (3).…”

Section: Resultsmentioning

confidence: 99%

“…We have found that one prophylactic dose of statolon, an interferon inducer derived from Penicilliwn stoloniferwn, has a protective duration of activity of 30 days against MM virus in mice (11). Statolon administered prophylactically IN 16 hr before infection has also been found to protect mice against influenza virus inoculated via the same route (8).…”

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confidence: 98%

“…The response to repeated doses of statolon has, therefore, been studied.MATERIALS AND METHODS Statolon. Statolon preparations similar to those previously described were employed (8,11,12). The statolon was dissolved in water.…”

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Inhibition of Influenza Virus and Interferon Response Intranasally with Statolon

Kleinschmidt

Streightoff

1971

Infect Immun

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Statolon, an interferon inducer, when instilled intranasally (IN) protects mice infected with lethal doses of influenza virus via the same route 16 hr later. The existence of interferon has been demonstrated in the trachea and lungs of mice treated IN with statolon, and it is assumed that the protection observed is due to this inhibitor. A dose response is seen with statolon administered IN. The protective activity of statolon instilled IN prophylactically lasts 1 to 2 weeks against influenza virus. Repeated doses of statolon, as many as four, a week apart, are effective. Antigenicity of the statolon (mycophage) particle relative to neutralization of its interferon-inducing capacity, therefore, may not prove to be a problem in clinical testing of this type of interferon inducer. The observed duration of activity of statolon also eliminates the possibility of difficulty due to hyporeactivity of the inducer.Once a viral infection is established, it is difficult to overcome with interferon inducers. Such inducers are more effective when administered prophylactically. A preferential route for administration of such inducers would be the intranasal (IN) route, a common portal of entry for many viruses. The fact that viruses are airborne even for relatively long distances (7) emphasizes the desirability of protection via this route.We have found that one prophylactic dose of statolon, an interferon inducer derived from Penicilliwn stoloniferwn, has a protective duration of activity of 30 days against MM virus in mice (11). Statolon administered prophylactically IN 16 hr before infection has also been found to protect mice against influenza virus inoculated via the same route (8). Because viruses have varying susceptibilities to interferon, determination of the duration of activity of statolon, instilled IN, against this respiratory virus was of interest relative to clinical application.Prophylactic use of an inducer invokes the necessity of repeated doses of the inducer. The double-stranded ribonucleic acid (DS-RNA)-containing mycophage particles (2,9,10), the predominant factor in statolon responsible for activity, are antigenic. A second dose of statolon could then be precluded from inducing interferon due to neutralization by antibody. The response to repeated doses of statolon has, therefore, been studied.MATERIALS AND METHODS Statolon. Statolon preparations similar to those previously described were employed (8,11,12). The statolon was dissolved in water. Concentrations of active statolon are based on nondialyzable solids.Treatment and infection of mice. Statolon in a volume of 0.05 ml, containing 300 ,g of the inducer, was administered with a syringe onto the noses of mice (ND4 strain, SPF), 11 to 13 g in weight, under light ether anesthesia. Control mice were treated with a saline solution. Sixteen hours later, the mice were infected with 10 LI),1 units of mouse-adapted PR8 influenza virus by aerosol. Infection was accomplished with a Tri-R aerosol infection apparatus capable of delivering aerosol particles appr...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Inhibition of Influenza Virus and Interferon Response Intranasally with Statolon

Kleinschmidt

Streightoff

1971

Infect Immun

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“…The MM virus is highly pathogenic for the common laboratory animals, such as the mouse, hamster, and cotton rat, when administered by various extraneural routes (1,6). It is stable under ordinary laboratory conditions (10) and is sensitive to interferon induced by statolon (8). Thus, it appears to be a very satisfactory representative of the encephalomyocarditis (EMC) group of viruses (2, 13, 14; J. Warren and J. E. Smadel, J.…”

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confidence: 99%

Propagation of MM Virus in Continuous Cell Lines

Pindak¹,

Schmidt²

1969

Applied Microbiology

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Baby hamster kidney (BHK), McCoy, and L cell lines were found to be suitable for isolation of MM virus from infected mouse brain tissue. The virus was recovered in high titer in the first passage in BHK and McCoy cells, with concomitant cytopathic effect (CPE). In L cells, virus yield was lower than in the other two cell lines and CPE was incomplete. Adaptation of the virus to BHK and McCoy cells by serial passages was evidenced by accelerated development of the CPE and increase in the virus titer. Plaques were obtained in all three cell lines when inoculated with infected mouse brain or with the tissue culture-propagated virus. In the BHK cells, the virus release preceded the appearance of CPE and maximal yield of virus was obtained after 1 to 3 days of incubation, depending on the size of inoculum. The BHK-propagated virus had the same lethality for mice as did the mouse brainpropagated stock, and there was no difference in the course of the disease caused by the two preparations.

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Is There Life Without Interferon?

Finter¹

1999

Interferon: The Dawn of Recombinant Protein Drugs

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Interferon induction with statolon in the intact animal.

Cited by 15 publications

References 12 publications

Inhibition of Influenza Virus and Interferon Response Intranasally with Statolon

Inhibition of Influenza Virus and Interferon Response Intranasally with Statolon

Propagation of MM Virus in Continuous Cell Lines

Is There Life Without Interferon?

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