Interferon inducers as antiviral agents

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Title Interferon inducers as antiviral agents
Publication Type dissertation
School or College School of Medicine
Department Biochemistry
Author Stringfellow, Dale Alan
Date 1972-08
Description Studies were undertaken to investigate factors which might influence the efficacy of interferon induces as antiviral agents. Initially, the kinetics of the interferon response induced in mice by poly I:C and tilorone hydrochloride was determined. The interferon response following oral administration of tilorone was unusually delayed and prolonged when compared with most synthetic inducers such a poly I:C but could not be explained on the bases of time required for absorption of the drug from the G.I. tract. Furthermore, although lymphatic tissue had been suggested to be a primary cell involved in the tilorone induced interferon response, treatment of mice with anti-lymphocyte serum had not effect on their ability to produce interferon in response to tilorone. These results indicated that lymphatic tissue were not critical in the tilorone induced interferon response as anticipated. Mice infected with Semliki Forest Virus or encephalomyocarditis (EMC) virus developed a progressive state of hyporeactivity to interferon induction. By 96 hours after infection with either virus, a time when symptoms of illness were first detectable, an 80 to 95% suppression of the interferon response could be demonstrated with all of the interferon inducers examined in these studies. This hyporeactive state was postulated to be one possible explanation for the observation that interferon inducers are less effective as antiviral agents when administered after the onset of the infection. Studies designed to evaluate the therapeutic efficacy of single or multiple injections of tilorone hydrochloride or poly I:C indicated that in order to successfully protect infected mice from the lethal consequences of EMC virus infection, suppression of a detectable viremia was essential. The viremia could be delayed or partially suppressed without protection. The data strongly suggest that once the CNS has been seeded and virus replication had begun inducer therapy was ineffective in altering the outcome of infection. This could in art be attributed to the low levels of interferon found in brain tissue following intraperitoneal administration of poly I:C. Also, animals which received the most effective treatment regimen of interferon inducers and survived the infection had a reduced incidence of circulating, neutralizing antibody. This reduction in the incidence of antibody in surviving mice was correlated with suppression of detectable viremia and presumably with prevention of sufficient antigenic stimulation to initiate the natural antibody response.
Type Text
Publisher University of Utah
Subject Exogenous; Leukocytes
Subject MESH Interferons; Antivenins
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Interferon inducers as antiviral agents." Spencer S. Eccles Health Sciences Library. Print version of "Interferon inducers as antiviral agents." available at J. Willard Marriott Library Special Collection. QR6.5 1972 .S77.
Rights Management © Dale Alan Stringellow
Format application/pdf
Format Medium application/pdf
Format Extent 4,005,859 bytes
Identifier undthes,5072
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship National Institutes of Health grant AI 10217 and contract NIH 70-2133.
Master File Extent 4,005,883 bytes
ARK ark:/87278/s6f76fb3
Setname ir_etd
ID 190828
Reference URL https://collections.lib.utah.edu/ark:/87278/s6f76fb3
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