BALTIMORE—Researchers at Johns Hopkins School of Medicine have discovered that aspirin inhibits interleukin 4 (IL-4), which is involved in allergic reactions and inflammation.[1] They believe that their discovery could eventually lead to the development of new treatments for asthma and allergies.

“Although aspirin has long been established as an anti-inflammatory drug, I would not discount the possibility of exploiting its immune-modulating potential,” Vincenzo Casolaro, MD, PhD, said to RESPIRATORY REVIEWS. “IL-4 is a major regulatory cytokine that is primarily involved in the development of allergic responses. By inhibiting IL-4 production, aspirin and related compounds might significantly affect the … strength of immune responses,” he said.

The new finding “might explain the previously observed antiviral properties of aspirin, as well as indicate its possible role in the attenuation of allergic inflammation,” added Dr. Casolaro, who is Assistant Professor of Clinical Immunology, Johns Hopkins School of Medicine.

For decades it has been known that aspirin inhibits prostaglandins and represses activation of nuclear factor kappaB (NF-kappaB), a molecular activator of cytokines; however, neither of these pathways fully accounts for the drug’s effectiveness in noninflammatory conditions.

In light of previous studies showing that aspirin interferes with cytokine gene expression, Dr. Casolaro and colleagues investigated whether aspirin might increase IL-4 production. They examined the effects of therapeutic concentrations of aspirin on the expression of effector cytokines in purified human CD4+ T cells. Contrary to their hypothesis, aspirin significantly reduced the expression of IL-4, but it did not affect the expression of other cytokines.

To determine whether inhibition of prostaglandin production might account for IL-4 suppression by aspirin, the researchers then compared the effects of different cyclooxygenase inhibitors on the expression of the cytokine. They found that this was not the case, making theirs the first study to document that T cells can be a direct target of aspirin. According to Dr. Casolaro, “Aspirin selectively represses the production of IL-4, but not of other T-cell cytokines. This confirms that the pathways regulating cytokine production in these cells significantly diverge at some level.” He added, “Aspirin is the first drug … found to selectively repress IL-4 generation.”

Although previous research showed that aspirin interfered with cell-mediated responses via inhibition of NF-kappaB, this was not the case in the present study. Dr. Casolaro believes the reason may be due to differences in the amount of aspirin used. “The concentrations of aspirin used in earlier studies were considerably higher than those commonly attained in the clinical setting.”

Although aspirin intolerance is common in people with asthma, symptoms result from cyclooxygenase inhibition. “We know that nonacetylated salicylates that do not affect cyclooxygenase activity are at least as effective as aspirin at inhibiting IL-4 production,” said Dr. Casolaro.

—Deborah L. O'Connor