Ethanol prevents development of destructive arthritis.
Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription factors. Mice exposed daily to this dose of ethanol did not display any liver toxicity, and the development of erosive arthritis was almost totally abrogated. In contrast, the antibody-mediated effector phase of collagen-induced arthritis was not influenced by ethanol exposure. Also, the major ethanol metabolite, acetaldehyde, prevented the development of arthritis. This antiinflammatory and antidestructive property of ethanol was mediated by (i) down-regulation of leukocyte migration and (ii) up-regulation of testosterone secretion, with the latter leading to decreased NF-kappaB activation. We conclude that low but persistent ethanol consumption delays the onset and halts the progression of collagen-induced arthritis by interaction with innate immune responsiveness.
Jonsson
Ing-Marie
IM
Department of Rheumatology and Inflammation Research and Center for Bone Research at the Sahlgrenska Academy, Göteborg University, SE-405 30 Göteborg, Sweden.
Verdrengh
Margareta
M
Brisslert
Mikael
M
Lindblad
Sofia
S
Bokarewa
Maria
M
Islander
Ulrika
U
Carlsten
Hans
H
Ohlsson
Claes
C
Nandakumar
Kutty Selva
KS
Holmdahl
Rikard
R
Tarkowski
Andrej
A
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control*; D015519:Bone Density / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D024043:Collagen Type II / Q000276:immunology; D000431:Ethanol / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000502:physiology; D013739:Testosterone / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000502:physiology
D024043:Collagen Type II; D015850:Interleukin-6; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D016753:Interleukin-10; D000431:Ethanol; D013739:Testosterone