male-femaleIn a new study, researchers found that women’s immune systems responded more strongly than men’s systems to flu vaccine.

Whether the women were old or young, they produced both more antibodies and a higher inflammatory cytokine count (a sign of potential immunological overreaction) than males. It seems that earlier research focused on how genes located on the sex chromosomes might affect the immune response to vaccination.

This new study, published in the Proceedings of the National Academy of Sciences, looked at the role of testosterone.

The results could help in the treatment of immunological overreactions and might explain reasons for women having a higher rate of autoimmune disease.

The study’s abstract isn’t too technical, but if it reads that way, just jump over it to my plain language summary.

Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females.

While the gender gap in immune reactions has long been known, the mechanism behind it has remained a mystery. But in this study, the scientists identified a handful of genes, apparently regulated by testosterone, that they think are a key part of the response mechanism. The higher the testosterone levels of a participant, the lower the immunological reaction to vaccination.

Generally speaking, women have stronger immune system responses than men and that means that they are less prone to bacterial, viral, fungal and other types of infection than guys. But that jazzed up immune systems is also more likely to overreact. When that happens, it can attack healthy tissue. That happens in an autoimmune disease such as lupus. Even in less life-threatening diseases like the flu it can cause potentially fatal post-flu complications, like a cytokine “storm” in which an overproduction of immune cells overwhelm the body’s normal functions.

So, it is in our genes – specifically a cluster of genes involved in fat metabolism that were also associated with the amount of antibodies and cytokines produced. These genes appear to be regulated by testosterone and the higher the testosterone level the lower the antibody response. So there, Mr. Tough Guy!

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