Chronic granulomatous disease (CGD) is a recessive disorder characterized by a defective phagocyte respiratory burst oxidase, life-threatening pyogenic infections and inflammatory granulomas. Gene targeting was used to generate mice with a null allele of the gene involved in X-linked CGD, which encodes the 91 kD subunit of the oxidase cytochrome b. Affected hemizygous male mice lacked phagocyte superoxide production, manifested an increased susceptibility to infection with Staphylococcus aureus and Aspergillus fumigatus and had an altered inflammatory response in thioglycollate peritonitis. This animal model should aid in developing new treatments for CGD and in evaluating the role of phagocyte-derived oxidants in inflammation.
The present study examined the effect of interleukin-11 (IL-11) in a murine model of bowel ischemia (BI). Prophylactic IL-11 administration in BI mice (induced by occluding the superior mesenteric artery for 90 min) was associated with significantly decreased morbidity and mortality. IL-11-treated mice demonstrated rapid recovery of intestinal mucosa as evidenced by an increase in mitotic activity and suppression of apoptosis in intestinal crypt cells as well as increased peripheral platelet and leukocyte counts primarily due to an increase in peripheral lymphocyte number in BI mice. In contrast to vehicle-treated mice, which uniformly developed thrombocytopenia after ischemic injury, no IL-11-treated BI mice developed thrombocytopenia during the experimental period. These data suggest a role for IL-11 in the treatment of gastrointestinal mucosal diseases due to a wide variety of causative injuries.
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