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 this complex is associated in some models with inflammatory tissue injury, our experience has suggested that stimulation of this complex might have beneficial effects in some cases of infection and sepsis.SK 107647 is a synthetic peptide that has been shown to stimulate neutrophil expression of CD11b, in both small and large animal models, without increasing circulating neutrophil rodent models of E. coli peritonitis and K. pneumoniae pneumonia. We are presently designing a three-part study that will evaluate the effects of SK 107647 in a canine model of peritonitis. In initial studies, we have shown that it is possible to reliably measure CD11b expression in this model. In subsequent studies, we determined the effects of SK107647 on neutrophil CD11b expression in the model. These pilot studies are ongoing to determine which preparation of SK 107647 will give us maximal CD11b expression. Once the pilor studies are completed, we plan to study the effects of SK 107647 in septic canines.
