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A new arthritis therapy with oxidative burst inducers

Hultqvist, Malin LU ; Olofsson, Peter LU ; Gelderman, Kyra LU ; Holmberg, Jens LU and Holmdahl, Rikard LU (2006) In PLoS Medicine 3(9). p.1625-1636
Abstract
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... (More)
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-alpha 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. (Less)
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type
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publication status
published
subject
in
PLoS Medicine
volume
3
issue
9
pages
1625 - 1636
publisher
Public Library of Science
external identifiers
  • wos:000241923800030
  • scopus:33749037178
ISSN
1549-1676
DOI
10.1371/journal.pmed.0030348.
language
English
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yes
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The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
id
ce8a630f-f70f-47d6-9a97-b93d493043e1 (old id 376826)
date added to LUP
2016-04-01 12:21:58
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2020-10-04 04:49:11
@article{ce8a630f-f70f-47d6-9a97-b93d493043e1,
  abstract     = {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-alpha 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.},
  author       = {Hultqvist, Malin and Olofsson, Peter and Gelderman, Kyra and Holmberg, Jens and Holmdahl, Rikard},
  issn         = {1549-1676},
  language     = {eng},
  number       = {9},
  pages        = {1625--1636},
  publisher    = {Public Library of Science},
  series       = {PLoS Medicine},
  title        = {A new arthritis therapy with oxidative burst inducers},
  url          = {http://dx.doi.org/10.1371/journal.pmed.0030348.},
  doi          = {10.1371/journal.pmed.0030348.},
  volume       = {3},
  year         = {2006},
}