Combined Extracts of Artemisia and Green Tea, Mitigated Alcoholic Gastritis Via Enhanced Heat-shock Protein 27 / 대한소화기학회지

BACKGROUND/AIMS: Several lines of evidence from epidemiologic and laboratory studies have shown that the consumption of Artemisia or green tea extracts (MPGT) is inversely associated with the risk of alcohol-induced damage and other chronic diseases. Supported by previous studies showing that the combined extract of Artemisia and green tea, MPGT, exerted significantly either antioxidative or anti-inflammatory actions against Helicobacter pylori-associated gastric diseases, it was hypothesized that MPGT can offer protection against alcoholic gastritis. METHODS: Ethanol was administered to induce gastric damage in Wistar rats, which had been pretreated with various doses of MPGT, to measure the rescuing action of a MPGT pretreatment against ethanol-induced gastric damage. In addition, the molecular mechanisms for the preventive effects were examined. RESULTS: The MPGT pretreatment (100, 300, and 500 mg/kg) alleviated the ethanol-induced gastric damage, which was evidenced by the significant decrease in calcium-dependent phospholipase A2, MAPKs, and NF-κB levels compared to ethanol alone. Furthermore, the MPGT pretreatment preserved 15-prostaglandin dehydrogenase, whereas cyclooxygenase-2 was decreased significantly. All of these biochemical changes led to the significant alleviation of alcohol-associated gastric mucosal damage. Ethanol significantly increased the TUNEL positivity in the stomach, but MPGT decreased the apoptotic index significantly, which was associated with significantly lower pathological scores of ethanol-induced mucosal ulcerations. The significant protective changes observed alcoholic gastritis with MPGT were related to the increased expression of cytoprotective genes, such as heat-shock protein (HSP)27, HSP60, and PDGF. CONCLUSIONS: The efficient anti-inflammatory, anti-apoptotic, and regenerative actions of MPGT make it a potential nutrient phytoceutical to rescue the stomach from alcoholic gastritis.

Expression and Significance of Monocyte Chemoattractant Protein-1 in Inflammatory and Non-Inflammatory Glomerulonephritis / 대한신장학회잡지

Monocyte chemoattractant protein-1(MCP-1) has been known to play a role in the pathophysiology of inflammatory glomerular diseases through selective monocyte attraction and activation. Immunohistochemical analyses were conducted to investigate the presence of MCP-1 and CD68 positive macrophages in 5 normal and 20 diseased kidneys which consisted of IgA nephropathy(IgAN, 9), membranous nephropathy(MGN, 6), and minimal change disease(MCD, 5). MCP-1 mRNA was evaluated in the renal tissue from 4 patients and 4 controls by RT- PCR. In addition, the levels of urine MCP-1 were measured by ELISA and the relationships among renal MCP-1 expression, renal CD68 positive macrophage infiltration, urine MCP-1 levels, and the extent of proteinuria were evaluated. Renal MCP-1 expression was upregulated and primarily localized in tubular cells. Higher CD68 positive macrophage infiltration was observed in IgAN but not in normal controls and non-inflammatory glomerular diseases. The MCP-1 mRNA expression was strongest in IgAN patients' kidney and followed by MCD, MGN, and normal controls. In IgAN, the urinary excretion of MCP-1 correlated with renal MCP-1 expression and 24 hour urine protein. The degree of CD68 positive macrophage infiltration tended to correlate with urine MCP-1 levels in IgAN patients. In conclusion, our data suggest that MCP-1 is likely to play an important role in the pathophysiology of IgAN and seems to play a trivial role in that of MGN or MCD.

A Case of Chinese Herbs Nephropathy / 대한신장학회잡지

No abstract available.

The Efficacy and Safety of Cyclosporin A(Cipol-N(R) soft capsule) in Adult Nephrotic Syndyrome: 16 Weeks, Open Label, Multicenter Study(Phase III Clinical Trial / 대한신장학회잡지

A multicenter prospective study was done in four-university hospital to evaluate the efficacy and safety of cyclosporin A(CyA, Cipol-N(R)) in 64 patients with adult nephrotic syndrome mean age 34.8 years, male:female 2.4:1, duration of disease 38.0+/-40.9months, 31 patients with MCD, 33 patients with Non-MCD (8 FSGS, 14 MGN, 7 MPGN, 2 lupus nephritis, 1 HBsAg associated GN)]. The prior steroid responses of these patients were 17 steroid dependent, 9 frequent relapser, 4 steroid resistant and 1 other in MCD patients, and 5 steroid dependent, 5 frequent relapser, 22 steroid resistant and 1 other in Non-MCD patients. After a 2-week steroid (predni-solon 10mg/day or deflazacort 12mg/day) run-in period, CyA 5mg/kg/day and prednisolone 10mg/day (or deflazacort 12mg/day) were administered for up to 16 weeks. Of the 64 patients enrolled, ll patients were dropped out prematurely due to adverse events or protocol violation. Of the 53 patients who completed the study, 27 had MCD and 26 had Non- MCD. High response (CR and PR) rate of 68% (36/53) were obtained with CyA treatment in all patients. Although the response rate in MCD was significantly higher than that in Non-MCD (89 vs. 46%, p<0.05) and response rates were significantly different according to the previous steroid responses by univariate analysis, only previous steroid responses affected the response to CyA significantly by Logistic multiple regression analysis (p=0.03, RR 7.08); responses were 84% (27/32) in steroid dependent and frequent relapser patients, and 37% (7/19) in steroid resistant patients. 24-hr proteinuria significantly decreased after 2 weeks and serum albumin and cholesteroi increased significantly after 4 weeks of treatment compared to baseline level. The serum creatinine level was not changed during the study. No serious and unexpected side event was observed. In conclusion, cyclosporine therapy is a safe and effective mode of treatment in patients with ne-phrotic syndrome, especially in those who need prolonged administration of steroids with resulting in unavoidable steroid complications such as frequent relapser and steroid dependent type. The patients with steroid resistant type and contraidications of steroid administration such as DM, aseptic bone neerosis etc. can also be candidates for this treatment.

Evaluation of Functional Renal Volume with 99mTc-DMSA SPECT in Patients with Diabetes Mellitus / 대한신장학회잡지

About 40% of patients with diabetes mellitus develops to diabetic nephropathy, and these patients show increment of glomerular filtration rate and renal volume at early phase. 99mTc-DMSA SPECT (single photon emission computed tomography) can measure a functional renal volume because 99mTc- DMSA it is taken up by the viable proximal tubular cells located in the renal cortex. To evaluate the renal volume in early diabetic nephropathy, we compared functional renal volume between diabetic patients and control, renal transplantation donor. 99mTc-DMSA was injected intravenously and SPECT was done after 2 hours in 15 diabetic patients, 18 renal transplantation donors, and 2 patients with end stage renal disease due to chronic glomerulonephritis. In diabetic patients with creatinine clearance more than 30ml/min and proteinuria, right and left renal volume were 247+/-22ml/BSA(m2), 256+/-37ml/BSA (m2), which were greater than those of diabetic patients with normal renal function and without proteinuria, or renal transplantation donors(P<0.05). In conclusion, we measured the functional renal volume by 99mTc-DMSA SPECT. Renal volume of diabetic patients with proteinuria were larger than the volume of control group or diabetic patients with normal renal function and without proteinuria. 99mTc-DMSA SPECT was thought to be useful test a for the measurement of functioning renal volume.

Difference of Urine MCP-1 in Inflammatory and Non-Inflammatory Glomerular Diseases and Its Realtion to the Proteinuria / 대한신장학회잡지

Monocyte chemoattractant protein-1(MCP-1) has been known to play a role in pathophysiology of inflammatory glomerular disease through selective monocyte attraction and activation. The levels of urine and serum MCP-1 in 20 inflammatory glomerular diseases(IgA nephropathy 16, lupus nephritis 4), 17 non-inflammatory glomerular diseases(membranous nephrothy 9, minimal change disease 8), and 10 normal controls were evaluated by ELISA. The secretion of MCP-1 by peripheral blood mononuclear cells(PBMC) was examined in 5 patients with IgA nephropathy, membranous nephropathy, and minimal change disease respectively and 5 normal controls. After 4 week treatment with steroid, the urine and serum MCP-1 levels were followed up in eighteen patients who received steroid therapy. Urinary excretion of MCP-1 was significantly higher in patients with inflammatory glomerular disease(0.78+/-0.51ng/mg creatinine) compared to normal controls(0.18+/-0.12ng/mg creatinine). There were no differences in serum MCP-1 levels and MCP-1 production by PBMC between normal controls and patients. Positive correlation between urinary excretion of MCP-1 and proteinuria were observed in the patients with inflammatory glomerular disease but not in the patients with non-inflammatory glomerular disease. Any correlation between serum MCP-1 levels and urinary excretion of MCP-1 or proteinuria was not found. Urinary excretion of MCP-1 and proteinuria were decreased after steroid therapy. However, reduction in urinary excretion of MCP-1 does not seem to be related with decrease in proteinuria. Further studies are necessary to clarify the clinical significances of reduction in urinary excretion of MCP-1 with steroid therapy. In conclusion, our data support some role of MCP-1 in the pathophysiology of inflammatory glomerular diseases. MCP-1, however, does not seem to play an important role in those of membranous nephropathy and minimal change disease.

Clinical usefulness of dipyridamole SPECT myocardial imaging in patients with end-stage renal disease / 대한내과학회지

BACKGROUND: Coronary artery disease(CAD) is a leading cause of death in patients with end-stage renal disease(ESRD). Current data concerning the role of dipyridamole SPECT myocardial imaging for the diagnosis of CAD in patients with ESRD vary according to authors. This study was performed to evaluate the usefulness of dipyridamole SPECT myocardial imaging and coronary angiography in diagnosing the CAD in patients with ESRD. METHODS: Sixty-three patients with ESRD underwent dipyridamole SPECT myocardial imaging and sixteen with positive myocardial imaging had selective coronary angiography. Controls were 73 patients with normal renal function who had dipyridamole SPECT myocardial imaging and coronary angiography because of chest pain or discomfort. The perfusion defect in myocardial images were defined as reversible or irreversible. Significant coronary artery disease was defined as one or more vessel disease with at least 50% stenosis on coronary angiography. The correlation between regional imaging defects and coronary stenoses in the corresponding vascular distribution was determined by the rule of a Van Train. RESULTS: Forty-nine of the patients had abnormal myocardial images (16 reversible, 6reversible + irreversible, 27 irreversible defects). Twenty six patients had a left anterior descending artery(LAD) defect, 13 a left circumflex artery(LCX) defect, 26 a right coronary artery(RCA) defect. There were no differences in age, sex, type and duration of dialysis, and associated atherogenic risk factors between patients with positive and negative myocardial imaging except for the durations of diabetes. Ten of the 16 patients, and thirty-nine of the 45 controls with positive myocardial imaging had a 50% or greater stenosis of one or more coronary arteries in coronary angiography. Therefore, the predictive value of positive SPECT in patients with ESRD was 63%, and that of controls was 87%. Of the 10 patients with stenotic lesions, 6 had double-, 3 single-, and 1 triple-vessel disease. Altogether, 7 diseased LCX , 6 RCA, and 5 LAD were found. In contrast, Of the 39 controls with angiographically significant stenotic lesions, 24 had single-, 9 double-, and 6 triple -vessel disease. Altogether, 27 diseased LAD, 17 LCX, and 16 RCA were found. There were no differences in age, sex, type and duration of dialysis, ST-T waves change, duration of ESRD, associated atherogenic risk factors, LV mass index and LVH between the patients with and without CAD except for the history of smoking. Three of 6 patients with false positive results of myocardial images had inferior perfusion defect and were on peritoneal dialysis. The pressure effects of peritoneal fluids on inferior perfusion defect were proven by a significant change of disappearance of inferior perfusion defect in myocardial images after complete drainge of the peritoneal fluids. And, the predictive value of positive SPECT differed between patients with and without false positive results of myocardial images (predictive value of positive SPECT 63% and 77%, respectively). CONCLUSION: Dipyridamole SPECT myocardial imaging appears to be an useful method for detection and exclusion of CAD in patients with ESRD and interpretation of dipyridamole SPECT myocardial imaging with inferior perfusion defect in patients with continuous ambulatory peritoneal dialysis needs more caution.

Cytokine Production by Peripheral Blood Mononuclear Cells in Renal Transplantation Rejection and Their Effect on Expressions of ICAM-1 and HLA Class II Antigen / 대한내과학회지

OBJECTIVES: We examined the levels of IL-1 , IL-6, TNF- , and IFN-gamma in peripheral blood mononuclear cells (PBMC) supernatants of kidney allograft recipients and also investigated the effect of PBMC supernatants on the expressions of HLA Class II antigen and ICAM-1 on endothelial cells. METHODS: PBMC were harvested before grafting, at steady state after grafting (serum creatinine < 2.0 mg/dL), at the onset of acute rejection episodes, and at steady state after rescue from acute rejection episodes. At each step, we examined the levels of cytokines in PBMC supernatants and investigated supernatants induced HLA class II antigen and ICAM-1 expression on cultured umbilical venous endothelial cells. RESULTS: HLA class II antigen and ICAM-1 expression were higher in endothelial cells stimulated with PBMC supernatants from uremic hemodialysis patients (N=10) than from control subjects (N=8). The levels of IL-1 , IL-6, TNF- , and IFN-gamma in PBMC supernatants were higher in uremic hemodialysis patients than in control subjects. In steady state after grafting, significant reductions in the PBMC supernatants induced HLA class II antigen and ICAM-1 expression on endothelial cells and the levels of these cytokines were found. In graft recipients who underwent rejection (N=5), cytokine production by PBMC and PBMC supernatants induced HLA class II antigen and ICAM-1 expression increased at the time of rejection and decreased after treatment of rejection but not significant. CONCLUSION: Cytokine production by PBMC and PBMC supernatants induced HLA class II antigen and ICAM-1 expression were higher in uremic hemodialysis patients than in normal controls. They significantly decrease in steady state after grafting and immunosuppressive therapy was considered as a major factor responsible for that. Further studies ,however, are still required to clarify the roles of cytokines, HLA class II antigen, and ICAM-1 in a series of allograft rejection process.

Long-Term Follow up of Thyroid Functions in Patients with Successful Renal Transplantation (RT) / 대한내과학회지

BACKGROUND: Thyroid status in uremia is still inconclusive due to the complexicity of the system. No single pathogenetic event may explain the thyroid function abnormalities in end stage renal disease (ESRD). Defects at all levels of the hypothalamic-pituitary-thyroid axis have been identified. Regarding the thyroid dysfunction in ESRD it is well recognized that the TSH response to TRH is blunted and serum concentrations of thyroid hormones are decreased in patients with ESRD. Whether or not on maintenance hemodialysis. Restoration of renal function with renal transplantation resulted in normalization of all parameters of thyroid function with exception of blunted TSH response to TRH. We evaluated the long-term changes of the thyroid function in 10 patients to know whether the thyroid function and the hypothalamo-pituitary axis were improved with the recovery of the renal function under maintenance low-dosage steroid administration after renal transplantation. METHODS: These tests were performed during the morning in the fasting state in 10 ESRD patients before, 1 month and 6 years after renal transplantation (RT). Thyroid function tests. Serum T3, T4 were measured by RIA kit and serum TSH was measured by IRMA kit. TRH stimulation test. Serum blood samples were obtained 0, 30, 60, 90, 120 min after TRH (400microgram) administration. Statistical analysis. All grouped data were expressed as mean+/-SD. Student t-test was used to assess the statistical difference between any two means. RESULTS: 1) The mean basal level of serum T3 was reduced in ESRD patients (53.6+/-33.2ng/dL) and increased to the low normal level 1 month after RT (87.8+/-25.4ng/dL), improved to the normal level 6 years after RT (116.3+/-28.8ng/dL). 2) The mean basal level of T4 was within normal range before RT (5.9+/-1.1microgram/dL), after 1 month (6.2+/-1.2microgram/dL) and after 6 years (6.5+/-1.4microgram/dL) of RT. 3) The mean basal level of TSH was within normal range before RT (2.0+/-1.2microU/mL), after 1 month (1.1+/-0.7microU/mL), and after 6 years (0.7+/-0.5microU/mL) of RT. Rut the mean TSH level of 6 years of RT was significantly decreased within the normal range. 4) In ESRD the TSH response to TRH was blunted, had a diminished peak and delayed fall before RT. After 1 month of RT, the TSH response to TRH was persistently blunted, however showed more rapid fall of TSH. After 6 years of RT, the TSH response to TRH normalized, but the absolute level of TSH and the peak level of TSH to TRH were less than before and after 1 month of RT. CONCLUSIONS: The abnormalities of thyroid hormones in uremic patients were improved partially after 1 month of RT and almost completely after 6 years of RT. But the level of T3H and the peak level of TSH to TRH were low within normal range, these results may be a direct consequence of low-dosage and long-term glucorcorticoid administration.

Effects of Mixed Leukocyte Reaction, Hydrocortisone, or Cyclosporine A on Expression of Adhesion Molecules by Endothelial and Mesangial cells / 대한내과학회지

OBJECTIVES: ICAM-1, VCAM-1, and betal integrins mediate cell-cell or cell-matrix interactions. We investigated effects of mixed leukocyte reaction (MLR), cyclosporine A (CsA), or hydrocortisone (HC) on their expression by endothelial (EnC) and mesangial cells (MC). METHODS: MLR was performed with or without CsA or HC for 5 days. After adding 25N MLR supernatant, cytokines or CsA to MC or EnC, the expression of VCAM-1, ICAM-1, and alpha3beta1 and a501 integrins was examined by using cell surface enzyme immunoassays or flow cytometry. RESULTS: MLR supernatant induced a marked increase in the expression of ICAM-1 and VCAM-1 on MC or EnC(p<0.001). HC treatment during MLR effectively inhibited MLR-induced upregulation of VCAM-1 and ICAM-1 on both cells (p<0.005). HC had, however, no inhibitory effect on VCAM-1 expression when added with MLR supernatant to cells. CsA treatment during MLR caused a modest decrease in MLR-induced expression of VCAM-1 on EnC, but had no effect on that of ICAM-1. INFgamma or TGFbeta1 stimulated expression of VCAM-1, and INFgamma, IL-1beta, or TNF alpha expression of ICAM-1 on MC after 24 hr. INFgamma, or TGFbeta1 enhanced expression of alpha3beta1 or alpha5beta1 integrins on MC after 5 days. CsA caused a modest decrease in basal expression of VCAM-1, and also decreased the basal, or INFgamma, or TGFbeta1-induced expression of alpha3beta1 and alpha5beta1 integrins on MC. CONCLUSION: Alloreactive lymphocytes and monocytes upregulate expression of VCAM-1 and ICAM-1 on EnC and MC maybe by secretion of cytokines such as INFgamma, and facilitate leukocytes attachment and following renal or vascular injury. HC effectively prevent the upregulation of VCAM-1 and ICAM-1 by inhibiting the release of cytokines during MLR. CsA did not cause an increase in the expression of VCAM-1 and beta1 integrin.

Clinical Study of Acute Renal Failure / 대한내과학회지

OBJECTIVE: Acute Renal Failure is a clinical syndrome characterized by a sudden decrease in renal function which was previously normal. Despite advances in medical care, prognosis in ARF is variable according to the influence of demographic factors, severity of ARF, nature of disease causing ARF, coexisting disease, treatments applied, and complications. We studied the recent changes of clinical feature of ARF. METHODS: We studied retrospectively 245 patients with ARF who had been hospitalized at Kyung Hee University Hospital between February 1988 and March 1993. RESULTS: 1) Male to female sex ratio was 1.8 : 1, and the incidence was high in above fifth decade (67.8%). 2) Acute renal failure was classified, according to clinical background, into medical group 79.6% (195 cases) and surgical group 20.4% (50 cases), and oliguric group 40.8% (100 cases) and non-oliguric group 59.2% (145 cases). 3) Acute renal failure due to medical causes included ARF by hemorrhagic fever with renal syndrome (25.6%), drugs and chemicals (17.9%), sepsis (17.4%) and systemic infection (7.7%) etc. ARF due to surgical causes included ARF by multiple trauma (34%), various surgical procedures (30%), surgical sepsis (14%), burn (12%) etc. 4) During admission, the expired patients had more severe biochemical and clinical characteristics including high BUN and serum potassium (p<0.01), lower serum albumin (p<0,01) than those of survivor. 5) Infections as the cause of ARF were 107 cases (43.7%), which included hemorrhagic fever with renal syndrome 50 cases, sepsis 31 cases, urinary tract infection 7 cases and respiratory tract infection 6 cases etc. The most common infecting organism was Hantavizus (50.5%). There was a greater number of gram-negative organisms than gram-positive organisms (34.1% vs 9.9%). 6) The overall mortality rate in patients with ARF was 31.4Fo. The presumptive causes of death were underlying disease (59.7%) such as sepsis, acute poisoning, cardiogenic and hypovolemic shock, and respiratory failure (14.3%), hyperkalemia (9.1%), pulmonary edeme (6.5%), and metabolic aidosis (2.6%) in order of frequency. 7) The highest mortality rate was 42.6% in patients above 50 years old. Mortality rate in patients with ARF due to surgical causes (52.0%) was significantly high than that of medical causes (26.2%) (p<0.05). Among the expired patients, oliguric group was 72.7%. In conclusion, there have been major trends in the clinical features of acute renal failure in this study. Especially, significant increase in the number of elderly patients, non-oliguric patients, and medical causes such as hemarrhagic fever with renal syndrome or sepsis were observed. Survival rate significantly decreased with increasing age, in acute renal failure by surgical causes, in oligurie patients, and in the presence of complicating factors such as sepsis or shock.

Post-renal Transplant Diabetes Mellitus-a Retrospective Study / 대한신장학회잡지

To investigate the clinical characteristics and predisposing factors for post-renal transplant diabetes mellitus (PTDM) in Kyung Hee University Medical Center, the records of all renal allograft recipients from 1985 through 1994 were reviewed. One hundred and seventy-nine nondiabetic recipients, whose allografts functioned longer than 6 months, were analyzed for the development of PTDM and the following results were obtained. Twenty two (12.3%) patients developed diabetes mellitus one week to 7 months after transplantation; sixteen of whom were diagnosed within the first 2 months of transplantation. Posttransplant diabetic patients were older (41+/-8.5 vs. 34.8+/-10.8, p<0.05) than those without PTDM. The prevalence of PTDM was significantly higher in patients who received grafts from unrelated donors (p<0.05). Mean fasting blood glucose level of diabetic group was higher than that of nondiabetic group but both of which were within normal range. In HLA phenotypes in 148 renal transplant recipients, the frequencies of HLA-Aw33, -Bw58, -DR7, and -DQw2 were higher in PTDM group, compared with non diabetic group. Family history of diabetes mellitus, the prevalence of posttransplant hypertension, the male to female ratio, and type of immune suppression were similar in both groups. To identify predisposing factors, 44 non diabetic patients matched for age, sex, and time of transplant were used as case controls. There were no differences in cyclosporine or cumulative steroid dose, weight gain after transplant, and graft function at the onset of diabetes between the patients with PTDM and case controls. Our data show that the incidence of PTDM is 12.3% and most of them develop within the first 2 months after transplantation. The risk of PTDM is higher in older patients and those with unrelated donor, higher fasting blood glucose levels, and those with HLA-Aw33, -Bw58, -DR7, DQw2 antigens. It appears to be independent of the amount of prednisone and/or cyclosporine employed.

Effects of mixed leukocyte reaction, hydrocortisone and cyclosporine on expression of leukocyte adhesion molecules by endothelial and mesangial cells

We investigated the effects of mixed leukocyte reaction (MLR), hydrocortisone (HC) and cyclosporine A (CsA) on the expression of leukocyte adhesion molecules on the mesangial (MC) and endothelial cells (EnC). Cell surface enzyme immunoassay showed that INFnu, IL-1beta, or TNF alpha stimulated expression of ICAM-1, or VCAM-1 on MC after 24 hours. Flow cytometric analysis demonstrated that MLR supernatant induced a marked increase in mean fluorescence of or % of cells highly expressing intercellular adhesion molecule(ICAM)-1 or vascular cell adhesion molecule (VCAM)-1 on both cells after 24 hours (p<0.001). HC treatment(300 ng/ml) during MLR effectively inhibited MLR-induced upregulation of ICAM-1 and VCAM-1 on both cells (p<0.005). When MLR supernatant with HC was added to adhesion molecule assay, there was no inhibitory effect of HC on VCAM-1. CsA treatment (500 ng/ml) during MLR caused a modest decrease in upregulation of VCAM-1 on EnC (p<0.05), but had no effects on ICAM-1 on both cells. CsA directly decreased expression of VCAM-1 on MC. In conclusion, alloreactive lymphocytes and monocytes upregulate the expression of VCAM-1 and ICAM-1 on target cells probably by the mediation of cytokines. HC effectively prevents MLR-induced upregulation of VCAM-1 and ICAM-1. CsA does not increase the expression of VCAM-1 and ICAM-1.

Effects of mixed leukocyte reaction, hydrocortisone and cyclosporine on expression of leukocyte adhesion molecules by endothelial and mesangial cells

We investigated the effects of mixed leukocyte reaction (MLR), hydrocortisone (HC) and cyclosporine A (CsA) on the expression of leukocyte adhesion molecules on the mesangial (MC) and endothelial cells (EnC). Cell surface enzyme immunoassay showed that INFnu, IL-1beta, or TNF alpha stimulated expression of ICAM-1, or VCAM-1 on MC after 24 hours. Flow cytometric analysis demonstrated that MLR supernatant induced a marked increase in mean fluorescence of or % of cells highly expressing intercellular adhesion molecule(ICAM)-1 or vascular cell adhesion molecule (VCAM)-1 on both cells after 24 hours (p<0.001). HC treatment(300 ng/ml) during MLR effectively inhibited MLR-induced upregulation of ICAM-1 and VCAM-1 on both cells (p<0.005). When MLR supernatant with HC was added to adhesion molecule assay, there was no inhibitory effect of HC on VCAM-1. CsA treatment (500 ng/ml) during MLR caused a modest decrease in upregulation of VCAM-1 on EnC (p<0.05), but had no effects on ICAM-1 on both cells. CsA directly decreased expression of VCAM-1 on MC. In conclusion, alloreactive lymphocytes and monocytes upregulate the expression of VCAM-1 and ICAM-1 on target cells probably by the mediation of cytokines. HC effectively prevents MLR-induced upregulation of VCAM-1 and ICAM-1. CsA does not increase the expression of VCAM-1 and ICAM-1.