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

我们在以前的一些研究中已经表明，在细菌攻击的脓毒症动物模型中，抑制CD 11/18粘附复合物对中性粒细胞的感染和结果。虽然这种复合物在某些模型中与炎性组织损伤有关，但我们的经验表明，刺激这种复合物在某些感染和败血症病例中可能具有有益作用。SK 107647是一种合成肽，已在小型和大型动物模型中显示其刺激中性粒细胞表达CD 11b，而不增加E. coli腹膜炎和K.肺炎我们目前正在设计一项三部分研究，该研究将评价SK 107647在犬腹膜炎模型中的作用。在最初的研究中，我们已经表明，在这个模型中可靠地测量CD 11b表达是可能的。在随后的研究中，我们确定了SK 107647对犬腹膜炎模型中中性粒细胞CD 11b表达的影响。这些初步研究正在进行中，以确定SK 107647的制备，这将使我们获得最大的CD 11b表达。完成后，我们计划研究SK 107647在脓毒症犬中的作用。

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.