Evaluation of Copovithane as a Nonspecific Immunomodulator in Surgically Simulated Sepsis

Abstract

Copovithane (CPV), a synthetic polymer, has been shown to have antitumor activity and also to reduce mortality in experimental murine peritonitis. The purpose of this study was to compare CPV with muramyl dipeptide (MDP), an immunomodulator of proven efficacy in simulated surgical infection. Six groups of CBA/J mice were compared; they received intramuscular injections of normal saline (controls), MDP (100 micrograms), or CPV (100, 200, and 400 mg/kg) 24 h prior to bacterial challenge. The challenge consisted of a Klebsiella-impregnated thigh suture. The first experiment assessed survival after bacterial challenge. The MDP and the CPV groups both had median survival times of 3 days, significantly longer than the control group (1 day, p less than .05). In the second experiment, animals were sacrificed at 6, 24, and 48 h following bacterial challenge, and blood and infected muscle were taken for quantitative bacteriology. At 6 h, there was no difference between groups. Both the MDP and CPV groups had significantly (p less than .05) lower blood bacterial counts than the control group at 24 and 48 h. Both the MDP and CVP groups had significantly lower local bacterial recovery than controls at 48 h (p less than .05), and local bacterial recovery of the MDP group was significantly lower than the control group at 24 h (p less than .05). CPV improved survival and reduced local and systemic bacterial recovery compared with controls. Although the effect of CPV was similar to MDP in this model, it consistently was of lower magnitude and had a narrow dose range.