Influence of MIP-1 Alpha on the CD4+ Th Lymphocytes

PURPOSE: MIP-1 alpha, initially identified as a substance to promote inflammation, was recently discovered to also suppress proliferation of many kinds of cells. In this study, the influence of MIP-1 alpha on CD4+ Th cells to secrete cytokines (IL-10, IL-2, IFN-gamma) and to express CD25 molecules was investigated. METHODS: Peripheral blood mononuclear cells (PBMCs) were prepared from five normal volunteers and initially divided into 4 groups: IL-10, IL-2, IFN-gamma, and CD25. Each group was further divided into 4 subgroups according to the incubation with or without MIP-1 alpha and to the incubation for 30 minutes or 3 hours. Analysis was performed by flow cytometry. RESULTS: Incubation of CD4+ Th lymphocytes with MIP-1 alpha showed a tendency to increase Th1 cytokine (IL-2, IFN-gamma) secretion and to decrease Th2 cytokine (IL-10) release, but there was no significant difference between any of the experimental groups. Among the CD4+ Th lymphocyte groups cultured with MIP-1 alpha, the expression of CD25 was significantly lower in the 3-hour incubation group than in the 30-minute group (P=0.008). CONCLUSION: MIP-1 alpha may play a role in facilitating immune response by increasing Th1 and decreasing Th2 cytokine secretion from CD4+ Th cells, and also by decreasing the proportion of CD4+CD25+ Th cells in the peripheral blood. However, in vivo study is necessary to verify the function of MIP-1 alpha in the living body.

Long Term Maintenance Immunosuppressive Therapy with Mycophenolate Mofetil and Steroid after Kidney Transplantation

PURPOSE: Cyclosporine associated hemolytic uremic syndrome (HUS) is a serious complications following kidney transplantation. In this study, 2 renal transplant patients, treated by the dual drugs -Mycophenolate Mofetil (MMF) and steroid (Deflazacort), without cyclosporine- due to development of HUS, were followed-up. Additionally, IFN-gamma and IL-10 as Th1 and Th2 cytokines, respectively, and their serum levels investigated. METHODS: Following their recovery from HUS, the 2 patients have been followed for 37 and 45 months, respectively, with MMF and steroid as maintenance immunosuppressants. The serum IFN-gamma and IL-10 levels were measured simultaneously in the 2 patients on dual drug, 10 on triple drug (cyclosporine, MMF, steroid) therapies and 18 normal volunteers. The 10 patients on the triple drug therapy were selected from 14 patients, that had undergone renal transplantations in the same year as the 2 dual drug therapy patients. RESULTS: At 37 and 45 months post-transplantation, the 2 pdual drug therapy patients showed serum creatinine levels less than 1.8 and 1.7 mg/dl, respectively. The serum IFN-gamma and IL-10 levels of the 12 (2 dual and 10 triple drug therapy) renal transplant patients (11.83+/-5.01 and 5.96+/-6.02 pg/ml, respectively) were significantly higher than those of the 18 normal volunteers (7.25+/-0.84 and 1.40+/-0.81 pg/ml, respectively), (IFN-gamma: P=0.000, IL-10: P=0.000). However a comparison of IFN-gamma and IL-10 levels between the 2 dual(11.56+/-3.35 and 4.91+/-1.66 pg/ml, respectively) and 10 triple drug therapy patients (11.89+/-5.43 and 6.17+/-6.61 pg/ml, respectively) showed no significant difference (IFN-gamma: P=0.606, IL-10: P=0.485). CONCLUSION: Long-term maintenance treatment with MMF and steroid is an effective alternative therapy in case of cyclosporine induced HUS.