| Rejection is the major obstacle to successful clinical intestinal transplantation (IT). This thesis examines the roles of cytokines, cytokine-inducible molecules, and lipopolysaccharide (LPS) in murine IT rejection. A unidirectional rejection murine model of IT was used to determine the temporal pattern of cytokine gene expression. Semiquantitative reverse-transcriptase polymerase chain reaction demonstrated early and persistent upregulation of IFN{dollar}gamma.{dollar} In contrast, IL-2, IL-4, IL-5, and IL-6 gene expression peaked early and decreased thereafter. Northern blot hybridization of IT allografts demonstrated upregulation of the proinflammatory cytokines TNF{dollar}alpha{dollar} and IL-{dollar}1beta{dollar} prior to the typical histologic features of rejection when compared to isografts. Parallel increases were seen in the cytokine-inducible molecules MHC class II and ICAM-1. Since proinflammatory cytokines are produced in large quantity by macrophages in response to LPS, IT were performed using mice with a genetic hyporesponsiveness to LPS. The tempo of rejection in these mice did not differ from their normal controls suggesting that LPS does not play a primary role in IT rejection. |
