We have shown in a number of previous studies that inhibition of the CD11/18 adhesion complex on neutrophils worsens infection and outcome in bacteria-challenged animal models of sepsis. Although in some models this complex is associated with inflammatory tissue injury, our experience suggests that stimulation of this complex might be beneficial in some cases of infection and sepsis. SK 107647 is a synthetic poly-peptide that has been shown in both small and large animal models to stimulate neutrophil expression of CD11b without increasing circulating neutrophil numbers. Administration of this peptide is protective in rodent models of Escherichia coli peritonitis and Klebsiella pneumoniae pneumonia. We are presently designing a three-part study to evaluate the effects of SK 107647 in a canine model of peritonitis. We will initially determine its effects on canine neutrophil CD11b expression as well as its toxicity in the canine model. If the agent does stimulate canine CD11b expression and is not associated with toxicity, we will then test it in the canine peritonitis model. This study has been submitted for ACUC approval and should start by November 1996.
