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 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.


RESULTS
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.
Hultqvist
Malin
M
Medical Inflammation Research, Lund University, Sweden.
Olofsson
Peter
P
Gelderman
Kyra A
KA
Holmberg
Jens
J
Holmdahl
Rikard
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018922:HL-60 Cells; D006801:Humans; D010836:Phytol / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects* / Q000502:physiology; D013729:Terpenes / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D017382:Reactive Oxygen Species; D013729:Terpenes; D010836:Phytol; C009042:pristane