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Am J Physiol Gastrointest Liver Physiol (October 21, 2004). doi:10.1152/ajpgi.00036.2004
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Submitted on January 22, 2004
Accepted on October 15, 2004

The Female Intestine is More Resistant Than the Male Intestine to Gut Injury and Inflammation When Subjected to Conditions Associated with Shock States

Hiroshi Homma1, Erik Hoy1, Da-Zhong Xu1, Qi Lu1, Rena Feinman1, and Edwin A. Deitch1*

1 Department of Surgery, UMDNJ - New Jersey Medical School, Newark, NJ, USA

* To whom correspondence should be addressed. E-mail: edeitch{at}umdnj.edu.

Having documented that proestrus female rats are more resistant to shock-induced acute gut and hence lung injury than male rats, we tested the hypothesis that the female gut is more resistant to injury and produces less of an inflammatory response than the male gut when exposed to conditions associated with shock states (hypoxia and acidosis) utilizing the ex-vivo Ussing chamber system. Ileal mucosal membranes harvested from normal male and female rats mounted in Ussing chamber systems were exposed to normoxia or 40 min of hypoxia at a normal pH (pH 7.3) or acidosis (pH6.8). Cytokine and nitric oxide levels in the serosal compartment of the Ussing chamber were measured at the end of the 3 hr hour experimental period to assess the immuno-inflammatory response, while FITC-dextran (MW 4,300) was employed to assess barrier function. Histo-morphological changes were used to quantitate gut mucosal injury. Hypoxia, acidosis or hypoxia plus acidosis was associated with a significant increase in pro-inflammatory cytokine production (IL-6, TNF, MIP-2) by the male as compared with the female intestinal segments. In contrast, the female gut manifested a higher anti-inflammatory response (nitric oxide and IL-10) and improved intestinal barrier function as well as less evidence of mucosal injury than the male intestinal segments. Administration of estradiol or the testosterone receptor antagonist, flutamide, to male rats abrogated the increase in gut injury and the increased IL-6 and MIP-2 response observed after hypoxia plus acidosis. These results suggest that gender differences in the ex vivo intestinal response to stresses, such as hypoxia and acidosis, exist and that the administration of estradiol or blockade of the testosterone receptor to male rats mitigates these gender-differences.




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