Bcl-2 mediates sex-specific differences in recovery of mice from LPS-induced signs of sickness independent of IL-6.

Chronic pulmonary diseases are more common in boys than in girls. Therefore, we investigated the differences in signs of sickness in male and female mice that were exposed to lipopolysaccharide (LPS) by intranasal instillation. Because apoptosis is important in the resolution of inflammation, we tested the hypothesis that reduced levels of Bcl-2, a regulator of apoptosis, may play a role in gender-specific differences in response to inflammation. Bcl-2 wild-type (+/+) female mice recovered from an LPS-induced drop in body temperature and loss in body weight significantly faster than male (+/+) mice. Female heterozygous (+/-) mice showed reduced Bcl-2 levels and exhibited a slower recovery than female (+/+) mice that was similar to the recovery pattern in male (+/+) and (+/-) mice. Interleukin-6 (IL-6) activity levels in the bronchoalveolar lavage fluid were higher in male than in female mice but were not different between (+/+) and (+/-) mice. We conclude that Bcl-2 plays a role in mediating the faster recovery of female (+/+) mice from LPS-induced signs of sickness independent of IL-6. These studies indicate that apoptotic mechanisms may be involved in gender-specific differences in chronic pulmonary diseases.