EFFECTS OF SK 107647, AN IMMUNOSTIMULATORY AGENT, IN A CANINE MODEL OF GRAM-NEGAT

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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 which has been shown in both small and large animal models to stimulate neutrophil expression of CD11b without increasing circulating neutro-phil rodent models of E. coli peritonitis and K. pneumoniae pneumonia. We are presently designing a three part study which 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 canine peritonitis model. These pilot studies are ongoing to determine the preparation of SK 107647 which will give us maximal CD11b expression. Once completed, we plan to study the effects of SK 107647 in septic canines.