In a recent study in mice [Jonsson IM et al. Proc Natl Acad Sci 2007], alcohol consumption prevented development of destructive arthritis. This anti-inflammatory and anti-destructive property of alcohol was mediated by down-regulation of leukocyte migration and up-regulation of testosterone secretion, with the latter leading to decreased NF-kappaB activation. The authors concluded that low but persistent alcohol consumption delays the onset and halts the progression of collagen-induced arthritis by interfering with innate immune responsiveness.

The EIRA (Epidemiological Investigation of Rheumatoid Arthritis) study is a population based case-control study of incident cases of RA among 1,419 subjects aged 18–70 years in a defined area of Sweden. The primary inclusion criterion was first time diagnosis of RA according the 1987 ACR definition. Controls were matched for sex, age, and residential area.

The objective of this subanalysis of data from the EIRA study, presented by PhD student Henrik Källberg of the Karolinska Institute, was to assess the relationship between alcohol consumption and the risk of developing rheumatoid arthritis (RA), as well as the risk of developing subtypes of RA defined by the presence or absence of antibodies toward citrullinated peptides (anti-CCP2). The potential for smoking or HLA-DRB1 SE alleles to modify these associations was also investigated.

DNA from 1,204 cases and 871 controls was examined for the presence of HLA-DRB1 shared epitope (SE) alleles. The cases were also classified with regard to presence or absence of anti-CCP2 antibodies. Gender-specific odds ratios for RA were calculated with 95% confidence intervals for subjects with different consumptions of alcohol (none, 3–5 units per week, >5 units per week), smoking, and HLA-DRB1 SE alleles, compared with subjects with less exposure to alcohol (0–3 units per week), using logistic regression models with adjustments made for possible confounders.

Increased alcohol consumption (>3 units per week) was associated with a decreased risk of developing RA (OR 0.5; 95% CI 0.4–0.7). There was evidence of a dose dependency in that the higher alcohol consumption lowered the risk of RA. The estimated odds ratio associated with alcohol consumption was about the same regardless of the presence of anti-CCP positive RA or anti-CCP negative RA. Furthermore, the association between alcohol consumption and RA was modified by both smoking and HLA-DRB1 SE alleles.

The results from the present study thus indicate that alcohol consumption is associated with a protective effect in relation to risk of developing RA, and that this effect is independent of anti-CCP status. The study points to the need to investigate mechanisms behind the protective effect of alcohol in both man and mice in order to understand the effect of life style on RA, and to identify new targets for therapy.