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

我们在之前的许多研究中表明，在细菌攻击的脓毒症动物模型中，抑制中性粒细胞上的CD11/18粘附复合物会恶化感染和结果。虽然这种复合物在某些模型中与炎症组织损伤有关，但我们的经验表明，刺激这种复合物可能对某些感染和败血症有有益的作用。SK 107647是一种合成肽，在小型和大型动物模型中均显示可以刺激CD11b的中性粒细胞表达，而不会增加大肠杆菌腹膜炎和肺炎克雷伯菌肺炎的循环中性粒细胞模型。我们目前正在设计一个由三部分组成的研究，将评估sk107647在犬腹膜炎模型中的作用。在最初的研究中，我们已经证明在该模型中可靠地测量CD11b表达是可能的。在随后的研究中，我们确定了SK107647对犬腹膜炎模型中中性粒细胞CD11b表达的影响。这些试点研究正在进行中，以确定SK 107647的制备将使我们获得最大的CD11b表达。一旦完成，我们计划研究SK 107647对脓毒症犬的影响。

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.