Ethanol prevents development of destructive arthritis

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 collageninduced 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-B 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.inflammation ͉ cytokines ͉ sex hormones ͉ antibodies ͉ immunity E xcessive alcohol consumption depresses the immune system and increases the propensity to severe bacterial infections, including pneumonia (1), tuberculosis (2), and bacterial peritonitis (3), and to viral infections (4-6). However, some epidemiological studies have suggested that light to moderate ethanol consumption has protective effects against several diseases including chronic heart diseases (7, 8) and ischemic stroke (9).Ethanol consumption has also been implicated in the pathogenesis of systemic lupus erythematosus (SLE), a complex autoimmune disease in the development of which environmental and genetic factors interact. Indeed, some investigators have found that exposure to ethanol is associated with a lower risk for developing SLE (10, 11), whereas others did not observe any effect of alcohol consumption on the incidence of SLE (12, 13). The association between ethanol and rheumatoid arthritis (RA) has been discussed in some studies, but definite conclusions could not be drawn (14-16). Studies so far have been of an epidemiological nature and therefore have not provided any hints about the biological mechanisms of environmental stimuli in the development of autoimmune disease. Our aim here was to assess whether low but persistent consumption of ethanol in quantities nontoxic to liver might affect the incidence and disease manifestation of collagen type II (CII)-induced arthritis (CIA), an established model of human RA. Our results suggest that ethanol intake delays the onset and halts the progression of destructive arthritis. Results Effect of Ethanol Consumption on Development of CIA.To assess whether ethanol drinking has any impact on the development of CIA, CII-immunized mice were provided w...

Protective Effects of Estradiol on Ethanol-Induced Bone Loss Involve Inhibition of Reactive Oxygen Species Generation in Osteoblasts and Downstream Activation of the Extracellular Signal-Regulated Kinase/Signal Transducer and Activator of Transcription 3/Receptor Activator of Nuclear Factor-κB Ligand Signaling Cascade

“…Despite recent data showing that low levels of alcohol consumption may have beneficial effects on bone (Jonsson et al, 2007;Wosje and Kalkwarf, 2007), it has been known for many years that chronic alcohol abuse can cause a variety of harmful effects on hematopoiesis (Heermans, 1998;Prakash et al, 2001), with consequent bone loss in both females and males, representing a significant risk factor for the development of osteoporosis (Chakkalakal, 2005). The molecular mechanisms underlying alcohol toxicity on bone cells, including both osteoblasts and osteoclasts, are not well understood.…”

Alcohol consumption promotes insulin sensitivity without affecting body fat levels

“…Alternatively, alcohol consumption may stimulate insulin sensitivity by decreasing inflammation. 37 Inflammation is one of the main problems in obesity-induced insulin resistance. In a model of arthritis, Jonsson et al [37]37 showed that ethanol decreased inflammation, which was associated with amelioration of arthritis in alcoholAlcohol consumption promotes insulin sensitivity J Hong et al consuming mice.…”

“…37 Inflammation is one of the main problems in obesity-induced insulin resistance. In a model of arthritis, Jonsson et al [37]37 showed that ethanol decreased inflammation, which was associated with amelioration of arthritis in alcoholAlcohol consumption promotes insulin sensitivity J Hong et al consuming mice. 37 Therefore, it is possible that alcohol improves insulin sensitivity by decreasing inflammation in tissues that regulate glucose metabolism, such as adipose tissue and skeletal muscle.…”

Response to commentaries

“…Andréasson mentions a Swedish animal study which provided evidence for a preventive effect on the risk of rheumatoid arthritis [5]. In addition, a recent metaanalysis indicates a dose-response effect of alcohol [6].…”