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Changes in circulating lymphocyte subpopulations and mitogen-stimulated response in a rat infusion model of
1Biomedical Technology Section, Defence and Civil Institute of Environmental Medicine, West Toronto, Ontario, Canada.
Objective:
To describe the alterations in circulating concentrations of immune cells as well as in in vitro mitogen-stimulated response in a recently developed rat model of intra-abdominal infection.
Design:
Randomized, controlled study.
Setting:
Government research facility.
Subjects:
Male Sprague-Dawley rats.
Interventions:
Infected animals received an intraperitoneal infusion of 6.0 x 10(8) colony forming units of Escherichia coli during 12 hrs, whereas control rats received a sterile inoculum. All experimental animals underwent laparotomy and peritoneal lavage at the end of the infusion period. Blood samples were obtained 12 hrs, 36 hrs, or 7 days after the onset of infusion. Splenocytes were concomitantly harvested and assayed for response to the mitogens phytohemagglutinin (PHA), concanavalin A (Con A), and lipopolysaccharides, as well as for production of interleukin (IL)-2.
Measurements And Main Results:
Infected rats showed a marked leukopenia (-82% for 36 hrs), with leukocyte counts returning to normal at 7 days. They also developed a marked lymphocytopenia throughout the study; this was achieved through comparable reductions in circulating T and B cells. Con A responses in both groups were similar for 7 days. In contrast, splenocytes from infected animals showed reduced responses to lipopolysaccharides (-64%) and PHA (-30%) for 36 hrs compared with control splenocytes. IL-2 production from mitogen-stimulated splenocytes was suppressed in infected rats to 66% of that of control rats for 7 days. Suppressed PHA responses were not restored to control values in the presence of IL-2. For all of the parameters assessed, control animals showed either no significant changes or relatively fewer changes than infected rats.
Conclusions:
This model of intra-abdominal infection is associated with changes in circulating concentrations of immune cells as well as with temporary functional defects in B and T cells, consistent with those often observed in patients with peritonitis. However, the role of IL-2 in limiting the adverse effects of infection in this experimental model seems to be limited. This model may be a useful tool in furthering our understanding of the pathophysiology of intra-abdominal infections and in assessing the efficacy of new therapeutic modalities.