Cyp11a1 promotes the first and rate-limiting step in the production of corticosteroids. These steroids have long been used to treat allergic diseases because they inhibit inflammation associated with the allergic reaction. Evidence in recent years, however, has indicated that corticosteroids may also activate immune cells associated with allergic reactions.
The researchers sensitized mice to peanuts so that they became allergic to the legume. When subsequently fed peanut protein, the mice experienced diarrhea and inflammation in the small intestine. Levels of Cyp11a1 increased, as did cytokine signaling molecules IL13 and IL17A, which are associated with allergic reactions.
When the researchers used aminoglutethimide (AMG) to inhibit the enzymatic activity of Cyp11a1 in the sensitized mice, it prevented allergic diarrhea and inflammation, and reduced levels of IL13 and IL17A. It also reduced the conversion of naïve T cells into allergic Th2 and Th17 subtypes.
“While we evaluated Cyp11a1 blockade in peanut allergy, it could likely have an effect in the full range of food allergies,” said Dr. Gelfand.