AIM: Semapimod is an experimental drug that strongly inhibits macrophages and stimulates the cholinergic anti-inflammatory pathway. The aim of this study was to evaluate the effect of semapimod on experimentally-induced acute intestinal ischemia-reperfusion syndrome in rabbits.METHODS: The experimental protocol included 16 adult male White New Zealand rabbits divided into two equal groups, A and B. Animals were subjected to 150 min of intestinal ischemia, followed by 30 min of reperfusion. At 30, 90 and 150 min after the onset of ischemia the animals in group A received i.v. placebo (2 mg/kg; Cytokine PharmaSciences Inc, PA, USA) and those of group B received i.v. semapimod (2 mg/kg; Cytokine PharmaSciences Inc, PA, USA). Blood samples were taken for plasma measurements of tumor necrosis factor-a (TNF-a), interleukin 1β (IL-1β) and interleukin 6 (IL-6) at 0, 60, 120 and 180 min after the onset of ischemia. At the same time points, wedge intestinal biopsies were taken for histopathological evaluation of mucosal injury. All data were analyzed by the non-parametric Mann-Whitney test as appropriate. The power effect of Semapimod was evaluated by mixed between-within Anova statistical analysis.RESULTS: Measurements of TNF-a and IL-1β levels showed significant differences between groups A and B at 120 min (P=0.004 and P=0.003 respectively) and at 180 min (P=0.001 and p<0.005 respectively). IL-6 values were lower in animals of group B but the differences were not significant. Intestinal mucosal injuries were significantly milder in animals of group B at 120 and 180 minCONCLUSION: Semapimod minimized intestinal mucosa injury and reduced the systemic inflammatory response during acute intestinal ischemia-reperfusion. Further studies are required to investigate the possible value of semapimod as a new pretreatment modality in acute vascular abdomen.