ScienceDaily (Jan. 15, 2009) — Scientists in the United Kingdom are reporting new evidence that humans can make their own salicylic acid (SA) — the material formed when aspirin breaks down in the body. SA, which is responsible for aspirin's renowned effects in relieving pain and inflammation, may be the first in a new class of bioregulators, according to a new study.
In the report, Gwendoline Baxter, Ph.D. and colleagues discuss how their past research revealed that SA exists in the blood of people who have not recently taken aspirin. Vegetarians had much higher levels, almost matching those in patients taking low doses of aspirin. Based on those findings, the researchers previously concluded that this endogenous SA came from the diet, since SA is a natural substance found in fruits and vegetables.
Now the group reports on studies of changes in SA levels in volunteers who took benzoic acid, a substance also found naturally in fruits and vegetables that the body could potentially use to make SA. Their goal was to determine whether the SA found in humans (and other animals) results solely from consumption of fruits and vegetables, or whether humans produce their own SA as a natural agent to fight inflammation and disease. The results reported in the study suggest that people do manufacture SA.
"It is, we suspect, increasingly likely that SA is a biopharmaceutical with a central, broadly defensive role in animals as well as plants," they state. "This simple organic chemical is, we propose, likely to become increasingly recognized as an animal bioregulator, perhaps in a class of its own."
What Aspirin does?
Aspirin, the world's most used non-steroidal anti-inflammatory drug, provides the mainstay of therapy for inflammatory musculoskeletal disorders and has been shown to be effective in the management and prevention of a wide variety of non-inflammatory conditions, including coronary and cerebral ischemia and possibly gastrointestinal cancer.
Since the 1970s, researchers have known that aspirin works, in part, by inhibiting prostaglandin, a hormone-like substance present in a variety of tissues and body fluids that has many roles, including causing contraction of smooth muscle and promoting inflammation. Specifically, aspirin inhibits an enzyme, cyclo-oxygenase (COX), that catalyzes the generation of prostaglandin from cell membrane fatty acid precursors. But the suppression of prostaglandin production could not fully account for aspirin's effectiveness because, after 15 minutes, aspirin is broken down in the body and becomes salicylic acid, a completely ineffective inhibitor of COX.
By 1994, aspirin was found to actually repress the activation of NF-ÊB, a molecular activator of cytokines, chemicals that trigger inflammation. Casolaro, an allergy researcher, wondered whether IL-4, a cytokine, was in this category. His tests showed that IL-4 was not, however, and, in fact, that NF-ÊB repressed IL-4 expression in immune system cells.
Putting the pieces of the puzzle together, Casolaro and his team embarked on a study to test the notion that aspirin might actually increase IL-4 production using T cells from healthy donor blood and culturing them in the presence of aspirin. To his surprise, aspirin significantly reduced IL-4.
"The bottom line was a paradox," he says. "We found that aspirin had the opposite effect of what we might have expected and was clearly acting in a completely novel way." In mapping the gene responsible for the production of IL-4, they found that aspirin targets part of a complex of DNA binding proteins that form on the IL-4 promoter, the region that regulates the quantity of protein manufactured.
"Before this study, we knew that, fundamentally, aspirin had at least two pathways of action, on COX and on NF-ÊB. This study is the first evidence that aspirin influences IL-4, and does so via a third, novel pathway," says Casolaro.
The researchers speculate that because IL-4 favors recruitment of inflammatory cells from the blood stream, a process implicated in rheumatoid arthritis and heart disease, suppressing IL-4 with aspirin may be one reason the drug protects against both conditions.
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