To consider the mechanism of reduction of proteinuria by cyclosporine A (CYA) in the patient with intractable nephrotic syndrome, the effect of CYA on proteinuria and anionic sites (AS) of the glomerular basement membrane (GBM) was studied in puromycin aminonucleoside (PA) nephrotic rats. In addition the rats exogenously given human recombinant interleukin-2 (hrIL-2) every day repeated the same proteinuria were used. The PA nephrotic rats were made by single injection of PA 150 mg/kg excrete of urinary protein as compared 10 mg/day of urinary protein in the controls. The increase of urinary protein in the PA rats was inhibited by CYA10-20 mg/kg administrated orally from the day of PA injection for 15 days. To evaluate AS, the kidney were treated with a polyethyleneimine (PEI) staining method and the deposits in the lamina rara externa (LRE) of the GBM were counted on the electron micrographs. On the 15th day, in the PA rats, AS decreased greatly but were normal in the CYA-treated rats. On one hand, rats injected of hr IL-2 2.5 X 10(5)U/rat intraperitoneally for 14 days showed slight proteinuria on the 14th day, and the proteinuria was also inhibited by oral administration of CYA 25 mg/kg. As reduced in the rats treated with hrIL-2 as well as PA. The findings indicate that the proteinuria in the PA nephrotic rats and rats treated with hrIL-2 might result from reduction of AS and that the improvement of proteinuria in these rats by CYA might be due to the recovery of AS in the GBM.

1990-03-01·Cancer research

Maintenance and cure of the L5178Y murine tumor-dormant state by interleukin 2: dependence of interleukin 2 on induced interferon-gamma and on tumor necrosis factor for its antitumor effects.

Article

作者: Wheelock, E F ; Chen, L P ; Suzuki, Y ; Liu, C M

We reported previously that treatment of peritoneal cell (PC) cultures prepared from mice which harbor L5178Y lymphoma cells in a tumor-dormant state in their peritoneal cavity with interleukin 2 (HuIL-2) stimulated antitumor cytotoxic activity in both the nonadherent and adherent populations derived from such cultures. We report here that HuIL-2 induced the production of murine gamma interferon (MuIFN-gamma) in these PC cultures and required Lyt-1-, Lyt-2-, and L3T4-expressing lymphocytes to do so. HuIL-2 required and synergized with this induced MuIFN-gamma to stimulate cytotoxic activity in the nonadherent PC and the MuIFN-gamma itself stimulated cytotoxic activity in the adherent PC. Cyclosporin A prevented both the induction of MuIFN-gamma and the development of antitumor cytotoxic activity in HuIL-2-treated PC cultures. An addback of exogenous MuIFN-gamma to HuIL-2-cyclosporin A-treated PC cultures and to the nonadherent subpopulation of such cultures, at a concentration which itself produced no antitumor effect, permitted HuIL-2 to induce its antitumor effect. We previously reported that MuIFN-gamma requires the action of murine tumor necrosis factor (MuTNF) to induce cytotoxic activity in PC cultures from tumor-dormant mice. We report here that HuIL-2 also requires the action of (MuTNF) to stimulate antitumor cytotoxic activity in PC cultures from tumor-dormant mice. These results indicate that HuIL-2 induces MuIFN-gamma and requires and synergizes with this MuIFN-gamma and with (MuTNF) to stimulate antitumor cytotoxic activity in PC cultures from tumor-dormant mice.

1990-03-01·Cancer research

Maintenance and cure of the L5178Y murine tumor-dormant state by interleukin 2: in vivo and in vitro effects.

Article

作者: Wheelock, E F ; Suzuki, Y ; Calkins, C E ; Okayasu, T ; Liu, C M ; Chen, L P

We studied the antitumor effects of recombinant human interleukin 2 (HuIL-2) in DBA/2 mice which harbor L5178Y lymphoma cells in a tumor-dormant state in the peritoneal cavity and in peritoneal cell (PC) cultures prepared from such mice. Intraperitoneal injection of 10,000 to 100,000 units of HuIL-2/day for 10 days eliminated tumor cells from 30-45% of the mice, whereas no mice became tumor-free in the phosphate-buffered saline-treated control group. In vitro, as little as 10 units/well HuIL-2 failed to stimulate cytotoxic activity in PC from normal mice. HuIL-2 directly stimulated antitumor cytotoxic activity in nonadherent but not in adherent PC cultures from tumor-dormant mice; however, treatment of whole PC from tumor-dormant mice with HuIL-2 resulted in the development of antitumor cytotoxic activity in the adherent PC population which were derived from such cultures. This suggests that the HuIL-2-treated nonadherent PC contributed to the cytotoxic activation of the adherent PC. Flow cytometric analysis of the PC from tumor-dormant mice revealed a polyclonal expansion of T-lymphocytes. Lyt-1+, Lyt-2+, and L3T4+ lymphocytes were all required for HuIL-2 to induce antitumor cytotoxic activity.

100 项与重组人白介素2腺病毒(Chengdu Huasun Biotechnology) 相关的药物交易

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