To elucidate the questions of why not all patients with hepatitis B virus (HBV) infection develop HBV membranous nephropathy (HBVMN), we first measured serum HBe circulating immune complex (CIC) during the acute nephrotic phase of HBVMN and in HBV carriers. We found that the level of HBe CIC was low in the HBVMN patients and absent either in HBsAg+/ HBeAg+ patients without HBVMN or HBsAg+/HBeAg- asymptomatic carriers. Second, we needed to characterize the cellular immune response to HBV in patients with HBVMN. However, lack of a suitable autologous effector/ target cell system makes a precise study of HBVMN pathogenesis difficult. In the present study, we established a model system by using autologous HBcAg-expressing Epstein-Barr-virus-immortalized lymphoblastoid cell lines (LCL) as stimulator/target cells. Both proliferative response after stimulation with HBcAg and cytotoxic activity against autologous HBcAg-expressing LCL of the peripheral blood T cells obtained from the HBVMN patients and HBsAg carriers could be measured. Using autologous HBcAg-expressing LCL as stimulator/target cells for the study of HBcAg-specific cytotoxic T lymphocytes, we found that HBVMN patients had lower cytotoxic activity than did both HBV carriers and HBsAg-/HBsAb+, HBeAg-/HBeAb+ children. From the in vitro cytokine production study of peripheral blood T cells after stimulation with HBcAg, we found that T-helper-cell-1 -related IL-2 and IFN-γ productions were very low in HBVMN patients but T-helper-cell-2-related IL-10 production was higher in HBsAg+/HBeAg+ patients with HBVMN than in those without HBVMN. Based on these findings, we conclude that HBVMN children seem to have an inadequate cellular immune response to HBcAg.
In this study, we investigated whether peritoneal dialysate interleukin-6 (IL-6) and IL-8 levels were elevated during peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients, with special reference to the high peritonitis occurrence (HPO) group. Serial measurements of IL-6 and IL-8 levels in dialysate before, during and after resolution of peritonitis were done in 13 CAPD patients with 15 episodes of peritonitis. Based on the peritonitis occurrence, 7 patients were assigned to the low peritonitis occurrence (LPO) and 6 patients to the HPO group. Marked elevation of IL-6 and IL-8 in drain dialysate occurred in the early period of peritonitis especially on the first 2 days in both groups. However, there were no significant differences between the groups in the levels of IL-6 and IL-8 in drain dialysate on the first day of peritonitis. However, the disappearance of peritoneal dialysate IL-8 level was faster in the LPO than in the HPO group. The decrease in IL-8 levels during peritonitis was faster than that of IL-6. Marked elevation of IL-6 and IL-8 in drain dialysate was found in the patient with peritonitis caused by Staphylococcus epidermides and mixed gram-negative bacilli. Therefore, we hypothesize that when peritonitis occurs too frequently in a short period in the HPO group, more IL-6 and IL-8 have been produced in the peritoneum contributing to the ongoing peritoneal injury and/or fibrosis.
Cord blood mononuclear cells (MNC) were isolated from 20 normal full-term newborns. These MNC were preincubated with either 50, 100, or 200 micrograms/ml Thymostimulin or without Thymostimulin. The interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) production, cytotoxicity, and lymphoproliferation and IL-2 receptor (Tac) expression were all significantly increased after Thymostimulin treatment. For evaluation of the in vivo effect, two combined-immunodeficiency patients defective on the thymic level, one with progressive BCG infection, and one with DiGeorge syndrome were used. Before Thymostimulin treatment, the patient's MNC did not produce sufficient amounts of IL-2 and gamma-IFN. The cytotoxicity and lymphoproliferation were also low. After Thymostimulin treatment, the IL-2 and gamma-IFN production, cytotoxicity, and lymphoproliferative response were enhanced. These results suggest that Thymostimulin may be beneficial in the clinical treatment of primary cellular immunodeficiency. The improved immune reactivity including cytotoxicity and enhanced IL-2 and gamma-IFN production in the Thymostimulin treatment also indicates that there may be a beneficial effect on the combination of chemotherapy and Thymostimulin.
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