Inhibition of Respiratory Virus Infection by Locally Applied Interferon

Tc, Merigan; Hall, T. S.; Reed, Sylvia E.; Tyrrell, D. A. J.

doi:10.1016/s0140-6736(73)90714-9

Cited by 242 publications

(101 citation statements)

References 5 publications

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“…The absorbance was measured at 214 nm and 280 nm. HuIFN-αN3 species of different compositions separated agreeing to the fact that there is relative hydrophobic pattern using RP-HPLC [27,28].…”

Section: Analysis Of Huifn-αn3 By Rp-hplcmentioning

confidence: 80%

Additive Effects of Water-Soluble Propolis (Greit 120) and Human Interferon Alfa (HuIFN-αN3) against Influenza Viruses in Vitro

Filipič¹,

Gradišnik²,

Adriana³

et al. 2018

JAST-A

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Influenza virus affects the respiratory tract in humans causing a range of distinct manifestations including fever, nasal secretions, cough, headaches, muscle pain and pneumonia, which could become violent and severe. It was found that influenza A viruses remain resistant to amantadine and rimantadin with high level of oseltamvir resistance. Therefore, there is a need for constant improvement of drugs active against resistant influenza viruses. Propolis has anti-influenza activity both in vitro and in vivo. Human leukocyte interferon (HuIFN-αN3) is a multi-subtype protein that displays an antiviral activity against influenza virus. In this study we elucidated the anti-influenza activity of the mixes of water-soluble propolis (WSP) (Greit 120) and HuIFN-αN3 at different ratios. Greit 120 polyphenols, total phenol acids and bioflavonoid were characterized by HPLC-UV-ESI-MS504971 and HuIFN-αN3 by reverse-phase high-performance liquid chromatography (RP-HPLC). Influenza A and B viruses were separately added to the LLC-MK2 cells treated with WSP (Greit 120) and HuIFN-αN3 alone or in proportions 1:1, 1:2 and 2:1. Plates were incubated and cytopathic effect was determined. The best results (ID 50 ) were obtained with the mix of 10% WSP and HuIFN-αN3 in proportion 1:2, showing ID 50 at 12 ± 0.2 µg/mL and 19 ± 0.6 µg/mL for influenza A and B viruses, respectively. When comparing anti-influenza activity of WSP (Greit 120)/HuIFN-αN3 with that of ribavirin, it was found that 1:2 was the optimal ratio for WSP (Greit 120)/HuIFN-αN3 (0.5 and 0.6 for influenza A and B, respectively). This new formulation of WSP (Greit 120) and HuIFN-αN3, showing better anti-Influenza activity, will definitely improve its application in flu infections.

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Section: Analysis Of Huifn-αn3 By Rp-hplcmentioning

confidence: 80%

Additive Effects of Water-Soluble Propolis (Greit 120) and Human Interferon Alfa (HuIFN-αN3) against Influenza Viruses in Vitro

Filipič¹,

Gradišnik²,

Adriana³

et al. 2018

JAST-A

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“…Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) (11). In this latter study, a prophylactic effect on the clinical disease induced by a rhinovirus infection was demonstrated.…”

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confidence: 80%

“…The large quantity of human leukocyte IF (approximately 14 x 106 U) used by Merigan et al (11) for prophylaxis of the rhinovirus infection in volunteers indicates the need for improved efficacy of IF. Our results obtained in an in vitro nasal epithelial cell culture system and in our nasal clearance studies in chimpanzees and volunteers suggest that the development of significant in vivo antiviral activity may depend on the method of IF application employed (6-9).…”

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confidence: 99%

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Antiviral Activity of Intranasally Applied Human Leukocyte Interferon

Greenberg

Harmon

Johnson

et al. 1978

Antimicrob Agents Chemother

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Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm 2 ) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction ( P < 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application.

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“…Some success has already been achieved by this approach. In studies in volunteers, the intranasal application of large quantities of human leukocyte interferon has been shown to reduce the symptoms of rhinovirus, but not those of influenza B illness, and topical application of polyinosinic acid:polycytidylic acid was shown to have some effect in reducing incidence of rhinovirus infections (5,8).Over the past few years a new class of lowmolecular-weight interferon inducers has been developed. The first to be tested was an alkylsubstituted propanediamine referred to as 6,9,10,12).…”

mentioning

confidence: 99%

Lack of Effect of an Interferon Inducer, N,N -Dihexadecyl- m -Xylylenediamine, on Rhinovirus Challenge in Humans

et al. 1979

Antimicrob Agents Chemother

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CP-28,888-27 and placebo nasal sprays were compared in 62 normal volunteers challenged with rhinovirus type 13 or 21 in two randomized, double-blind studies. Half of the subjects received CP-28,888-27 and half received nasal placebo administered at 24, 20, and 16 h before challenge and 4 and 8 h after challenge. In each study, the number of subjects shedding virus in nasal washes, the number developing fourfold or greater serum antibody responses, and the number developing afebrile or febrile upper respiratory tract illness were not significantly different comparing subjects given CP-28,888-27 and those given placebo. Interferon was detected in nasal washes from 5 of 15 volunteers tested in the CP-28,888-27 group compared to 2 of 15 volunteers from the placebo group.The use of exogenous interferon or interferon inducers to control respiratory viral infections appears attractive because of the diversity of viral families and serotypes that produce common cold syndromes. Some success has already been achieved by this approach. In studies in volunteers, the intranasal application of large quantities of human leukocyte interferon has been shown to reduce the symptoms of rhinovirus, but not those of influenza B illness, and topical application of polyinosinic acid:polycytidylic acid was shown to have some effect in reducing incidence of rhinovirus infections (5,8).Over the past few years a new class of lowmolecular-weight interferon inducers has been developed. The first to be tested was an alkylsubstituted propanediamine referred to as 6,9,10,12). More recently, a related compound, N,N-dihexadecyl-m-xylylenediamine, purported to be more effective in animals than CP-20,961 and referred to as CP-28,888-27, has been developed (John Niblack, personal communication). We evaluated this drug in experimental rhinovirus infection in volunteers. Drugs. The substituted xylenediamine, CP-28,888-27, was supplied by Central Research, Pfizer, Inc., in multiple-dose spray containers with 50 mg of drug per ml in vehicle. Because of its insolubility, the drug was fused with equal weights of polysorbate 80 and glycerol and then homogenized in hot buffered (pH 7) 0.14 M NaCl, yielding a particle size <2 im in diameter in the homogenate. The spray apparatus was calibrated to deliver 1 il/dose in large particles (>25 p.n in diameter) to the nasal mucosa. Identical containers with only the vehicle were provided. Drug or placebo was administered at 24, 20, and 16 h before virus challenge and at 4 and 8 h after challenge. MATERIALS AND METHODSChallenge virus. Rhinovirus inocula were prepared in WI-38 human lung fibroblasts and were shown by inoculation of various tissue cultures after specific neutralization to be free of extraneous viruses (7). Rhinovirus type 21 was used in the study performed in Gainesville, and type 13 was used in Rochester. The challenge virus was given to the volunteers by nose drops, 0.25 ml in each nostril, containing three 50% tissue culture infectious doses (TCID50) of rhinovirus type 21

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Inhibition of Respiratory Virus Infection by Locally Applied Interferon

Cited by 242 publications

References 5 publications

Additive Effects of Water-Soluble Propolis (Greit 120) and Human Interferon Alfa (HuIFN-αN3) against Influenza Viruses in Vitro

Additive Effects of Water-Soluble Propolis (Greit 120) and Human Interferon Alfa (HuIFN-αN3) against Influenza Viruses in Vitro

Antiviral Activity of Intranasally Applied Human Leukocyte Interferon

Lack of Effect of an Interferon Inducer, N,N -Dihexadecyl- m -Xylylenediamine, on Rhinovirus Challenge in Humans

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