Ethanol prevents development of destructive arthritis

doi:10.1073/pnas.0608620104

Ethanol prevents development of destructive arthritis

*Department of Rheumatology and Inflammation Research and
^†Center for Bone Research at the Sahlgrenska Academy, Göteborg University, SE-405 30 Göteborg, Sweden; and
^‡Section for Medical Inflammation Research, Lund University, S-221 00 Lund, Sweden

Edited by Michael Sela, Weizmann Institute of Science, Rehovot, Israel, and approved November 9, 2006 (received for review September 29, 2006)

Abstract

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-κB 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.

Footnotes

^§To whom correspondence should be addressed at:
Department of Rheumatology and Inflammation Research, Guldhedsgatan 10, S-413 45 Göteborg, Sweden.
E-mail: andrej.tarkowski{at}rheuma.gu.se
Author contributions: H.C., C.O., R.H., and A.T. designed research; I.-M.J., M.V., M. Brisslert, S.L., M. Bokarewa, and U.I. performed research; C.O., K.S.N., and R.H. contributed new reagents/analytic tools; I.-M.J., M. Brisslert, S.L., M. Bokarewa, and U.I. analyzed data; and I.-M.J., M. Brisslert, M. Bokarewa, and U.I. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
Abbreviations:

RA,

rheumatoid arthritis;

CII,

collagen type II;

CIA,

CII-induced arthritis;

IQR,

interquartile range;

N.S.,

not significant;

IGF1,

insulin-like growth factor;

pQCT,

peripheral quantitative computed tomography;

BMD,

bone mineral density.