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A New Arthritis Therapy with Oxidative Burst Inducers

BACKGROUND: Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypot...

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Autores principales: Hultqvist, Malin, Olofsson, Peter, Gelderman, Kyra A, Holmberg, Jens, Holmdahl, Rikard
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1564167/
https://www.ncbi.nlm.nih.gov/pubmed/16968121
http://dx.doi.org/10.1371/journal.pmed.0030348
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author Hultqvist, Malin
Olofsson, Peter
Gelderman, Kyra A
Holmberg, Jens
Holmdahl, Rikard
author_facet Hultqvist, Malin
Olofsson, Peter
Gelderman, Kyra A
Holmberg, Jens
Holmdahl, Rikard
author_sort Hultqvist, Malin
collection PubMed
description BACKGROUND: Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypothesis that reactive oxygen species (ROS) promote inflammation was challenged when polymorphisms in Ncf1, that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. Based on these findings we developed a new therapy for arthritis using oxidative burst-inducing substances. METHODS AND FINDINGS: Treatment of rats with phytol (3,7,11,15-tetramethyl-2-hexadecene-1-ol) increased oxidative burst in vivo and thereby corrected the effect of the genetic polymorphism in arthritis-prone Ncf1 (DA) rats. Importantly, phytol treatment also decreased the autoimmune response and ameliorated both the acute and chronic phases of arthritis. When compared to standard therapies for RA, anti-tumour necrosis factor-α and methotrexate, phytol showed equally good or better therapeutic properties. Finally, phytol mediated its effect within hours of administration and involved modulation of T cell activation, as injection prevented adoptive transfer of disease with arthritogenic T cells. CONCLUSIONS: Treatment of arthritis with ROS-promoting substances such as phytol targets a newly discovered pathway leading to autoimmune inflammatory disease and introduces a novel class of therapeutics for treatment of RA and possibly other chronic inflammatory diseases.
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spelling pubmed-15641672006-09-14 A New Arthritis Therapy with Oxidative Burst Inducers Hultqvist, Malin Olofsson, Peter Gelderman, Kyra A Holmberg, Jens Holmdahl, Rikard PLoS Med Research Article BACKGROUND: Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypothesis that reactive oxygen species (ROS) promote inflammation was challenged when polymorphisms in Ncf1, that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. Based on these findings we developed a new therapy for arthritis using oxidative burst-inducing substances. METHODS AND FINDINGS: Treatment of rats with phytol (3,7,11,15-tetramethyl-2-hexadecene-1-ol) increased oxidative burst in vivo and thereby corrected the effect of the genetic polymorphism in arthritis-prone Ncf1 (DA) rats. Importantly, phytol treatment also decreased the autoimmune response and ameliorated both the acute and chronic phases of arthritis. When compared to standard therapies for RA, anti-tumour necrosis factor-α and methotrexate, phytol showed equally good or better therapeutic properties. Finally, phytol mediated its effect within hours of administration and involved modulation of T cell activation, as injection prevented adoptive transfer of disease with arthritogenic T cells. CONCLUSIONS: Treatment of arthritis with ROS-promoting substances such as phytol targets a newly discovered pathway leading to autoimmune inflammatory disease and introduces a novel class of therapeutics for treatment of RA and possibly other chronic inflammatory diseases. Public Library of Science 2006-09 2006-09-12 /pmc/articles/PMC1564167/ /pubmed/16968121 http://dx.doi.org/10.1371/journal.pmed.0030348 Text en © 2006 Hultqvist et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hultqvist, Malin
Olofsson, Peter
Gelderman, Kyra A
Holmberg, Jens
Holmdahl, Rikard
A New Arthritis Therapy with Oxidative Burst Inducers
title A New Arthritis Therapy with Oxidative Burst Inducers
title_full A New Arthritis Therapy with Oxidative Burst Inducers
title_fullStr A New Arthritis Therapy with Oxidative Burst Inducers
title_full_unstemmed A New Arthritis Therapy with Oxidative Burst Inducers
title_short A New Arthritis Therapy with Oxidative Burst Inducers
title_sort new arthritis therapy with oxidative burst inducers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1564167/
https://www.ncbi.nlm.nih.gov/pubmed/16968121
http://dx.doi.org/10.1371/journal.pmed.0030348
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