Induction of interferon in human subjects by poly I:C

Our plain-English summary of Induction of interferon in human subjects by poly I:C, by A.K. Field, C.W. Young, I.H. Krakoff, et al (Proceedings of the Society for Experimental Biology and Medicine, 1971).

The study

• Authors: A.K. Field, C.W. Young, I.H. Krakoff, A.A. Tytell, G.P. Lampson, M.M. Nemes, M.R. Hilleman
• Journal: Proceedings of the Society for Experimental Biology and Medicine
• Published: 1971;136(4):1180-6
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Poly I:C (rIn:rCn), a synthetic double-stranded polynucleotide previously demonstrated to be a potent inducer of interferon and host resistance to viral infection in cell culture and in animals, has been successfully used to induce interferon in human beings. Fourteen of 20 patients with advanced cancer developed interferon after a single intravenous administration of poly I:C. The interferon was identified by the usual criteria of pH stability, host species specificity, broad antiviral spectrum, inactivation by trypsin, and nonsedimentability under defined conditions. Several of the patients were capable of repeated induction of interferon by poly I:C at intervals of 3 to 7 days. Evidence of refractoriness to induction occurred only after repeated daily injections of poly I:C. The only consistent clinical manifestation of poly I:C administration was a febrile response. None of the patients tested developed demonstrable CF antibodies against either poly I:C or denatured DNA during the course of treatment.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

In plain English

This article is not about asbestos. It reported findings from 20 patients with far-advanced cancer given intravenous poly I:C, a synthetic double-stranded polynucleotide, at 2 to 4000 micrograms per kilogram. Fourteen of the 20 developed interferon, an antiviral substance, in their blood, and six did not. The response did not appear to be strongly related to dose. Interferon appeared as early as 2 hours after injection and usually peaked at 12 to 48 hours. Some patients responded again to injections given 3 to 7 days apart. One patient given increasing daily doses became hyporesponsive, meaning less responsive, after the fourth dose and was fully responsive again after a 10-day period. The authors could not define this refractory period precisely. Fever was the only consistent clinical reaction. Serum was tested from 19 patients, and none showed complement-fixing antibodies against poly I:C or denatured DNA at serum dilutions of 1:5 and greater. The authors cautioned that advanced cancer might have hidden minor toxic effects, and that possible immune deficiencies in cancer patients called for caution with the antibody results. One patient had mesothelioma, but asbestos is not mentioned.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Clinical trial in cancer patients, with retrospective laboratory study of blood samples taken before, during and after poly I:C treatment
• Who was studied: 20 patients with far-advanced cancer of various types (Memorial Hospital and Sloan-Kettering Institute, New York, with the Merck Institute). The results table lists one patient with mesothelioma. Dates of treatment are not given.
• Exposure: Intravenous poly I:C (an interferon inducer) at 2 to 4000 micrograms per kilogram. No asbestos exposure is studied.
• Main results:
  • 14 of the 20 patients produced serum interferon after a single injection: 9 from a zero starting titer and 5 from a pre-existing titer of 4. Six patients failed to respond.
  • Whether a patient responded, and how strongly and for how long, did not appear to be strongly related to dose within the doses tested.
  • Interferon appeared as early as 2 hours after injection and in some patients lasted at least 72 hours. The peak was at 12 to 48 hours.
  • Two patients responded again to injections at 6- to 7-day intervals, and one patient responded again within 3 days.
  • One patient (614634), given a series of increasing daily doses, showed hyporesponsiveness (reduced responsiveness) after the fourth dose of 200 micrograms per kilogram. This patient was fully responsive again after a 10-day period.
  • Fever was the most consistently repeatable response. Temperature rose by 0 to 7 degrees Fahrenheit, peaking 6 to 15 hours after injection.
  • Laboratory tests showed no disturbance of liver, kidney or bone marrow function.
  • Serum from 19 patients was tested by complement fixation. None showed antibody against poly I:C or heat-denatured DNA at serum dilutions of 1:5 and greater. Seven of these patients had received multiple doses and were bled over a period that would reasonably permit an antibody response.
  • The antiviral substance in selected serum samples was identified as interferon by standard criteria.
• The authors' conclusion: The authors concluded that poly I:C successfully induced interferon in human beings and that refractoriness occurred only after repeated daily injections. They said poly I:C may be regarded as relatively nontoxic for man, while cautioning that the patients had far-advanced cancer.
• Limitations the authors state:
  • The data were insufficient to define the number of injections and amount needed to cause hyporesponsiveness, or how long the refractory period lasts.
  • Far-advanced cancer in the patients might have obscured minor toxic effects that could be seen in healthy people.
  • The antibody results need caution because cancer patients may have immune deficiencies.
  • The group of patients was small.

Related studies

• Depression of viral interferon induction in cell monolayers by asbestos fibers — N. Hahon, H.L. Eckert (1976)
• Coinhibition of viral interferon induction by benzo[a]pyrene and chrysotile asbestos — N. Hahon, J.A. Booth (1986)
• Antitumor activity of type III interferon alone or in combination with type I interferon against human non-small cell lung cancer — H. Fujie, T. Tanaka, et al. (2011)
• Reduced cell viability and apoptosis induction in human thyroid carcinoma and mesothelioma cells exposed to cidofovir — S. Catalani, F. Palma, et al. (2017)
• Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms — Z.G. Fridlender, J. Sun, et al. (2010)
• In vitro biologic responses to native and surface-modified asbestos — N. Hahon, V. Vallyathan, et al. (1986)

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