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 m ice that were exposed to lipopolysaccharide (LPS) by intranasal instillatio n. Because apoptosis is important in the resolution of inflammation, we tes ted 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 bo dy temperature and loss in body weight significantly faster than male (+/+) mice. Female heterozygous (+/-) mice showed reduced Bcl-2 levels and exhib ited a slower recovery than female (+/+) mice that was similar to the recov ery pattern in male (+/+) and (+/-) mice. Interleukin-6 (IL-6) activity lev els 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 fr om LPS-induced signs of sickness independent of IL-6. These studies indicat e that apoptotic mechanisms may be involved in gender-specific differences in chronic pulmonary diseases.