Could a glass of wine at dinner time be the next major arthritis breakthrough?
Possibly... according to a recent Swedish study. A diet of 10% ethanol had a protective effect on mice that would otherwise have developed collagen-induced arthritis (CIA), Swedish researchers report in Proceedings of the National Academy of Sciences. CIA is often used as an animal model of human rheumatoid arthritis (RA.)
Andrej Tarkowski, MD, the senior author and a faculty member in the department of rheumatology and inflammation research, Goteborg University, in Sweden, stated that the primary finding was that, in male mice, long term consumption of 10% ethanol delayed the onset and progression of CIA.
The underlying mechanism appears to be a reduction in inflammation due to decreased NF-kB activation (a primary inflammatory pathway) caused by upregulation- or increased production -of testosterone secretion.
The research team fused a CIA model in mice by immunizing male DBA/1 mice with collagen type II (CII). To determine whether drinking ethanol has any impact on the development of CIA, the mice were provided with either 10% ethanol or water alone to drink. Mice were sacrificed after 5 to 6 weeks. All four paws from DBA/1 mice were sectioned, stained, and examined for inflammation of the joint including damage to the joint lining and erosion of bone and cartilage.
The investigators report that development of arthritis due to inflammation was markedly reduced in the ethanol-drinking mice. Ethanol had no such effect on mice with arthritis induced by injection with a mixture of four monoclonal anti-CII antibodies. "These data suggest that ethanol affects the start or initiation rather than the perpetuation of immune responsiveness during CIA," mentioned the researchers.
Joints from the water-drinking mice developed frequent bone and cartilage erosions. Those from the ethanol-drinking mice were "histologically ...intact," meaning no significant damage occurred. In addition, ethanol prevented the arthritis-induced loss of bone mineral density associated with CIA.
"The major surprise in this study was the outstanding effect of ethanol on saving cartilage and bone, suggesting that apart from regulation of inflammatory mediators, matrix metalloproteinases (i.e., tissue destroying enzymes) might be a direct target for ethanol," commented Dr. Tarkowski.
Dr. Tarkowski cautions, "This dose of ethanol was chosen for mice with an exact knowledge regarding the toxicity. This was further confirmed by intact liver function at the end of experiments. In contrast, exchanging water for 10% ethanol in humans eventually will lead to liver disease (cirrhosis). Thus, the optimal dose of ethanol in the human setting to prevent/delay RA is presently unknown. For practical purposes, one could speculate on the use of doses of ethanol similar to those sometimes suggested for prevention of cardiovascular diseases--i.e., something in the range of 1 to 2 glasses of wine per day," he suggested.
"We are presently analyzing whether female mice with arthritis have the same effect from ethanol.
The investigators also compared castrated to intact male mice and found that mice drinking 10% ethanol had significantly elevated levels of testosterone and decreased levels of IGF1 and cortisol. "These observations, considered together with the cellular anti-inflammatory properties of testosterone that lead to a decrease of NF-kB activation, point to testosterone as a potential link mediating the anti-inflammatory effects of ethanol."
So... what are the implications for patients with RA?
The first is that perhaps, a prescription of a glass or two of wine a day is not necessarily bad.
However, there are cautions. The first is that patients who are taking methotrexate need to absolutely limit their consumption of alcoholic beverages because of the danger of developing cirrhosis. Second, patients taking non-steroidal anti-inflammatory drugs are at increased risk for developing stomach ulcers and alcohol increases that risk.
(Jonsson I-M, Verdrengh M, Brissiert M, et al. Ethanol prevents development of destructive arthritis. PNAS. 2007;104:258-263)
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