Individual behavioral differences in recovery from abdominal sepsis in rats

Objective and Design:  In the present study we determined whether individual behavioral differences (high and low locomotor activity) differentially affected recovery from sepsis with high or low mortality. Methods:  Two trials were performed. Trial 1 with high mortality: Rats were randomly assigned to (1) control-A: anesthesia, (2) control-B: sham surgery, (3) sepsis: laparotomy and peritoneal contamination and infection (PCI) with human stool bacteria, (4) sepsis with antibiotic prophylaxis (cefuroxime/ metronidazole), and (5) sepsis with antibiotic plus G-CSF prophylaxis. Trial 2 with low mortality: Comparison of groups 3 and 5. Endpoints were mortality, behavior (open field and social interaction tests), and proinflammatory cytokines (interleukin-6 = IL-6 and macrophage inflammatory protein-2 = MIP-2). Results:  The combination of antibiotics plus G-CSF was most effective in reducing mortality in both trials and modified sickness behavior. Behavioral deficits were not statistically significantly improved by G-CSF. However, high versus low responders were differentially affected in both behavioral tests. Furthermore, IL-6 and MIP-2 were increased 24 hours after inoculum only in high responders with untreated sepsis and high mortality. Conclusion:  Improvement of sickness behavior in sepsis with G-CSF/antibiotic prophylaxis is a promising approach. The course of recovery from sepsis may depend on premorbid individual differences. Received 26 September 2008; returned for revision 25 October 2008; received from final revision 13 November 2008; accepted by M. J. Parnham 19 November 2008