Short and long term outcome of percutaneous coronary intervention with drug eluting stent and bare metal stent in patients with chronic kidney disease.

AIM: Coronary artery disease represents the most important cause of mortality and morbidity in chronic kidney disease (CKD). Despite continuous improvements in percutaneous coronary intervention (PCI), CKD is still associated with more adverse events after PCI. We performed a retrospective study to compare bare metal stents (BMS) versus drug eluting stents (DES) in CKD. METHODS: We included consecutively all patients undergoing PCI at our Centre from July 2002 to December 2005 with CKD, defined as creatinine clearance <60 mL/min. Patients who received only DES were compared to those who received only BMS. The primary end-point was the long-term rate of major adverse cardiac events (MACE, i.e. the composite of death, myocardial infarction and repeat revascularization). RESULTS: We included a total of 219 patients with CKD out of a total of 2354 patients, with 164 receiving BMS and 55 DES. After a mean follow up of 48 months, the MACE rate was significantly higher in BMS group (71% versus 38%, P<0.001). A similarly increased risk with BMS was found for death (45% versus 17%, P<0.001), whereas the rates for repeat coronary revascularization, myocardial infarction and stent thrombosis were not significantly different. Multivariable analysis showed that BMS vs.. DES implantation was not statistically significant associated with MACE, death, myocardial infarction, rePTCA or stent thrombosis. CONCLUSION: Compared with BMS, use of DES in patients with CKD is safe and effective in reducing adverse outcomes. However, differences found between groups in clinical end-point could be ascribed to selection bias and confounding factors.

IL-12, as an adjuvant, promotes a T helper 1 cell, but does not suppress a T helper 2 cell recall response.

IL-12 is a potent inducer of NK and cytolytic T cell activity, IFN-gamma production, and T cell proliferation, and is necessary for differentiation of naive T cells to the Th1 subset. We have previously shown that IL-12 promotes a primary Th1 response and suppresses a primary Th2 response in lymph nodes of mice primed with a model hapten-protein conjugate, 2,4,6-trinitrophenyl (TNP)-keyhole limpet hemocyanin (KLH). We have now extended these studies to determine the Th phenotype of the recall response following immunization with soluble Ag and IL-12. For these experiments, mice were primed with TNP-KLH with or without treatment with IL-12, allowed to progress beyond the primary immune response, and challenged by i.p. injection of TNP-KLH. The phenotype of the recall response was monitored by measuring ex vivo production of IFN-gamma and IL-4 in Ag-stimulated lymph node and spleen cell cultures. Titer and isotype of TNP-specific serum Abs were also evaluated. Mice primed with Ag+IL-12 developed a Th1 recall response, as detected by KLH-specific IFN-gamma production from cultured spleen cells and the presence of TNP-specific IgG2a Ab in serum. However, they also developed an Ag-specific Th2 recall response, as characterized by Ag-induced IL-4 production from spleen cells and the presence of high titers of anti-TNP IgG1 in the serum. Studies of the cytokine profile during the primary response revealed that IL-12 induced in spleen cells the capacity to express both IL-4 and IFN-gamma. CD4+ T cells are necessary for production of IL-4 in the spleens of IL-12-treated mice, and most likely account for the Th2 recall response detected in mice primed with Ag+IL-12. These results indicate that the Th1 phenotype induced by immunization with IL-12 and Ag is maintained so that a Th1 recall response is expressed upon subsequent challenge with Ag. However, immunization with IL-12 also supports the development of a Th2 recall response, indicating that the Th1-inducing effect of IL-12 in vivo is not accompanied by a long lasting suppression of Th2 development.

Immunoglobulin isotype modulation after administration of IL-12.

We have begun a series of experiments assessing the role of IL-12 in the humoral immune response. IL-12 is known to enhance cellular immunity causing a shift toward a Th1, as opposed to a Th2, response. IL-12 is also a potent stimulator of IFN-gamma production which, among other activities, modulates isotype expression particularly with respect to IgG2a. We have performed a series of experiments involving the concurrent dosing of mice with murine IL-12 and TNP-KLH followed by the monitoring of IgG1 and IgG2a anti-TNP responses and total IgG1 and IgG2a levels. Following administration of IL-12, specific anti-TNP titers showed an IgG2a increase while IgG1 responses were markedly lower than those exhibited by animals which did not receive IL-12. Total IgG1 levels in IL-12 treated mice remained at or near baseline while untreated mice demonstrated an increase in total IgG1 levels. In addition, lymph nodes from these mice were removed, stimulated with KLH and assayed for expression of murine IFN-gamma and IL-4. Murine IFN-gamma levels in supernatants obtained from IL-12 treated mice were elevated over those seen in untreated mice while IL-4 levels were suppressed.