Previous research has shown that women experience anaphylaxis – an allergic reaction prompted by food, medication or insect stings and bites – more often than men, but the mechanism behind this has been unclear. Now, a new mouse study suggests it may be down to estrogen.

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Researchers found the airways of male (right) and female (left) mice respond differently to anaphylactic triggers; the female response shows more accumulation of fluids and cells around the respiratory tract (arrows).
Image credit: NIAID

The researchers, from the National Institute of Allergy and Infectious Diseases (NIAID) – part of the National Institutes of Health (NIH) – publish their findings in The Journal of Allergy and Clinical Immunology.

They explain that immune cells in the body – mast cells in particular – release enzymes that trigger swelling of tissues and widening of blood vessels, causing the skin to flush or develop a rash. Additionally, this can prompt trouble breathing, shock or heart attack.

For their latest study, the researchers wanted to investigate any sex-dependent differences in mice in which they induced anaphylaxis to explore how female sex hormones may be involved.

They induced anaphylaxis in both female and male mice by using histamine, as well as Immunoglobulin E (IgE) or Immunoglobulin G (IgG) – types of antibodies – receptor aggregation. Then, the team monitored body temperature, release of mast cell mediators and lung weight as a means of assessing anaphylaxis.

Overall, the researchers observed that the female mice experienced anaphylactic reactions that were more severe and longer lasting than those of the male mice.

They found that estradiol, which is a type of estrogen, influences blood vessels and enhances the levels and activity of endothelial nitric oxide synthase (eNOS), an enzyme that drives anaphylaxis

Interestingly, when the team blocked eNOS activity, they found that this gender difference vanished. Additionally, when they blocked estrogen in female mice, this reduced the severity of their allergic responses, bringing them down to a level observed in the male mice.

The results could solve the mystery of why women frequently have allergic reactions that are more severe than those of men.

Commenting on their findings, the researchers write:

”Our study defines a contribution of estrogen through its regulation of eNOS expression and nitric oxide production to vascular hyperpermeability and intensified anaphylactic responses in female mice, providing additional mechanistic insights into risk factors and possible implications for clinical management in the further exploration of human anaphylaxis.”

They add that their results shed further light on the importance of accounting for gender in animal experiments.

Although the study established a link between estrogen and eNOS in severe anaphylactic reactions in the female mice, the team says further research needs to be conducted into whether such effects are similar in humans, and whether these findings can be applied toward preventive treatments.

Medical News Today recently reported on a study from Johns Hopkins University in Baltimore, MD, that identified a protein as the culprit in allergic reactions to a range of drugs. Researchers from that study said their findings could be used to create drugs that enable better treatment for patients with prostate cancer, diabetes and HIV.