Innate immune responses in children and adults with shigellosis

An array of pro- and anti-inflammatory mediators of the innate immune syste m was analyzed in stool, urine, and rectal mucosa samples from adults and c hildren with shigellosis to better understand their role in recovery from a nd in the immunopathogenesis of the disease. Increased concentrations of la ctoferrin (Lf), myeloperoxidase (MPO), prostaglandin E-2, and leukotriene B -4 (LTB4) in stool during acute shigellosis in both children and adults ind icated that activated cells of the innate defense system at the mucosal sit e were secreting the mediators. Increased concentration of MPO and 8-iso-pr ostaglandin F-2 alpha and lower levels of superoxide dismutase (SOD) activi ty in stool during acute Shigella infection suggested increased formation o f reactive oxygen species, free radical-catalyzed peroxidation of membrane lipids, and decreased scavenging of the reactive oxygen radicals. In childr en, lower expression of SOD in tissue with severe inflammation and lower le vels of SOD activity in stool for longer periods compared to adults may fur ther worsen the tissue damage and predispose the children to a lowered defe nse. Both adult and pediatric patients had significantly higher expression of inducible nitric oxide synthase (iNOS) in the rectum with severe inflamm ation, compared to that seen,with mild inflammation, accompanied by persist ently up-regulated iNOS mRNA, reflecting increased production of nitric oxi de at the local site. However, in contrast to adults, reduced urinary nitra te levels in pediatric patients during acute shigellosis suggested lower pr oduction of nitric oxide in the renal compartment, Persistent production of Lf in pediatric patients may contribute to chronic inflammation in the rec tum, In addition, increased production of proinflammatory mediators in the rectum of patients with severe histology suggested contribution of these mo lecules to the immunopathogenesis of severe colitis caused by shigellae.