Men may recover more quickly from influenza infections because they produce more amphiregulin (AREG), a growth factor protein important in wound healing, scientists at Johns Hopkins Bloomberg School of Public Health reported in a paper published today in Biology of Sex Differences.
The team infected live mice and human cells derived from male humans with influenza virus, and found that both the male mice and human cells produced more amphiregulin. The male mice recovered more quickly, compared to female mice, whereas male mice lacking amphiregulin had recovery times close to those of females.
Researchers have known that women tend to have more severe flu with slower recoveries even when their virus levels are the same. It had been thought that this was due solely to women's greater levels of lung inflammation during flu infections. "The novel finding here is that females also have slower tissue-repair during recovery, due to relatively low production of amphiregulin," says senior study author Sabra Klein, Ph.D., an associate professor in the department of molecular microbiology and immunology.
For the study, Klein and her team infected mice with a non-lethal dose of H1N1, an Influenza A strain that caused a global pandemic in 2009-10 with more than 18,000 deaths. They observed that although male and female mice had similar levels of virus and cleared it in about the same amount of time, the females suffered significantly more from their infections. They had greater loss of body mass and greater lung inflammation during the acute phase of infection, and later they were slower to recover normal lung function.
The scientists identified amphiregulin as a key factor in this gender-based difference. The growth-factor protein is known to promote the proliferation of epithelial cells in the skin, lung and other surfaces in the body during wound healing, including recovery from lung infections. Analysis of the mice revealed that the males produced significantly more amphiregulin than females during the recovery phase of their infections.
Moreover, male mice that had been genetically engineered to lack amphiregulin showed the same pattern as females, with more severe infections and slower recoveries. Females without amphiregulin were relatively unchanged in their infection severity, suggesting that the lung-healing protein makes a difference primarily for males.