EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS

This article presents the results of immunotoxicity study of a novel slow-release drug for multiple sclerosis treatment based on recombinant human interferon beta-1а. The test article is polyethylene glycol (PEG)-conjugated interferon beta-1a. Performed modification allows to improve pharmacokinetic...

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Autores principales:	A. B. Dzheliya, Ya. Yu. Ustyugov, M. A. Kortava
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2015
Materias:	multiple sclerosis interferons t lymphocytes b lymphocytes natural killer cells сd69 antigen immunoglobulins Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/572806fba477489c9191f0392523ba81
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spelling	oai:doaj.org-article:572806fba477489c9191f0392523ba812021-11-18T08:03:45ZEVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS1563-06252313-741X10.15789/1563-0625-2015-4-319-326https://doaj.org/article/572806fba477489c9191f0392523ba812015-10-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/923https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XThis article presents the results of immunotoxicity study of a novel slow-release drug for multiple sclerosis treatment based on recombinant human interferon beta-1а. The test article is polyethylene glycol (PEG)-conjugated interferon beta-1a. Performed modification allows to improve pharmacokinetic parameters, decrease immunogenicity and elevate tolerance that significantly increases safety of the test article. The study is performed in nonhuman primates – rhesus monkeys (Macaca mulatta). The species, used in this study, is susceptible to human interferon beta-1a that has previously been shown in specific activity studies. Dynamics of peripheral blood lymphocyte subsets composition, activated lymphocyte count (based on the presence of early activation marker), serum antibodies (IgM, IgG, IgA and IgE) level and ratio were assessed within in vivo experiments. The effect of interferon beta-1a on CD69 expression was examined in mononuclear cells culture. It was shown that the test article causes changes in lymphocyte subsets ratio (decrease of NK-cells relative count with T-lymphocytes relative count elevation) in primates’ peripheral blood. Revealed changes were reversible and dose-independent. It was not shown that the test article have reliable effect on CD69 expression rate. There was no evidence of test article effect on level and ratio of serum antibodies and polymorphonucleocytes phagocytic rate in the absence of additional antigenic exposure. The results obtained during the experiment indicate the absence of pathological effect of the test article on the nonhuman primates’ immune system.A. B. DzheliyaYa. Yu. UstyugovM. A. KortavaSPb RAACIarticlemultiple sclerosisinterferonst lymphocytesb lymphocytesnatural killer cellsсd69 antigenimmunoglobulinsImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 17, Iss 4, Pp 319-326 (2015)
institution	DOAJ
collection	DOAJ
language	RU
topic	multiple sclerosis interferons t lymphocytes b lymphocytes natural killer cells сd69 antigen immunoglobulins Immunologic diseases. Allergy RC581-607
spellingShingle	multiple sclerosis interferons t lymphocytes b lymphocytes natural killer cells сd69 antigen immunoglobulins Immunologic diseases. Allergy RC581-607 A. B. Dzheliya Ya. Yu. Ustyugov M. A. Kortava EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS
description	This article presents the results of immunotoxicity study of a novel slow-release drug for multiple sclerosis treatment based on recombinant human interferon beta-1а. The test article is polyethylene glycol (PEG)-conjugated interferon beta-1a. Performed modification allows to improve pharmacokinetic parameters, decrease immunogenicity and elevate tolerance that significantly increases safety of the test article. The study is performed in nonhuman primates – rhesus monkeys (Macaca mulatta). The species, used in this study, is susceptible to human interferon beta-1a that has previously been shown in specific activity studies. Dynamics of peripheral blood lymphocyte subsets composition, activated lymphocyte count (based on the presence of early activation marker), serum antibodies (IgM, IgG, IgA and IgE) level and ratio were assessed within in vivo experiments. The effect of interferon beta-1a on CD69 expression was examined in mononuclear cells culture. It was shown that the test article causes changes in lymphocyte subsets ratio (decrease of NK-cells relative count with T-lymphocytes relative count elevation) in primates’ peripheral blood. Revealed changes were reversible and dose-independent. It was not shown that the test article have reliable effect on CD69 expression rate. There was no evidence of test article effect on level and ratio of serum antibodies and polymorphonucleocytes phagocytic rate in the absence of additional antigenic exposure. The results obtained during the experiment indicate the absence of pathological effect of the test article on the nonhuman primates’ immune system.
format	article
author	A. B. Dzheliya Ya. Yu. Ustyugov M. A. Kortava
author_facet	A. B. Dzheliya Ya. Yu. Ustyugov M. A. Kortava
author_sort	A. B. Dzheliya
title	EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS
title_short	EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS
title_full	EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS
title_fullStr	EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS
title_full_unstemmed	EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS
title_sort	evaluation of immunotoxicity of the therapeutic drug prolonged action for multiple sclerosis on rhesus monkeys
publisher	SPb RAACI
publishDate	2015
url	https://doaj.org/article/572806fba477489c9191f0392523ba81
work_keys_str_mv	AT abdzheliya evaluationofimmunotoxicityofthetherapeuticdrugprolongedactionformultiplesclerosisonrhesusmonkeys AT yayuustyugov evaluationofimmunotoxicityofthetherapeuticdrugprolongedactionformultiplesclerosisonrhesusmonkeys AT makortava evaluationofimmunotoxicityofthetherapeuticdrugprolongedactionformultiplesclerosisonrhesusmonkeys
_version_	1718422417469079552

EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS

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