caa a22 4500 475772547 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s001250051480 doi (NATIONALLICENCE)springer-10.1007/s001250051480 Cyclophosphamide inhibits the development of diabetes in the diabetes-prone BB rat [Elektronische Daten] [D. O. Sobel, B. Ahvazi, H.-S. Jun, Y.-H. Chung, J.-W. Yoon] Abstract : Aims/hypothesis. Cyclophosphamide has been shown to augment the diabetic process in NOD mouse and BB rat models of Type I (insulin-dependent) diabetes mellitus. Because cyclophosphamide has, however, been shown to increase immunoregulatory cell activity, we examined if cyclophosphamide treatment increases immunoregulatory cell activity and inhibits the diabetic process in BB rats. Methods. The development of insulitis and diabetes was explored in BB rats treated with saline and cyclophosphamide (60 to 175 mg/kg body weight). Subsets of spleen cells were assessed by flow cytometry and cytokine gene expression by RT-PCR. To determine if cyclophosphamide induces immunoregulatory cell activity, the development of diabetes was assessed in BB rats injected with spleen cells from rats treated with saline and cyclophosphamide. Results. All dosages of cyclophosphamide decreased the development of diabetes. The degree of insulitis was lower in pancreata from 55-day-old rats treated with cyclophosphamide than those from controls. Cyclophosphamide caused no alterations in the numbers of NK cells, T-cell subsets, or RT6.1+ T cells. The adoptive transfer of spleen cells from cyclophosphamide-treated rats to BB rats inhibited the development of diabetes. Cyclophosphamide treatment decreased IL-12, IL-1β, IL-2, IFN-γ and TNF-α gene expressions in mononuclear spleen cells but IL-4 gene expression increased. Conclusion/interpretation. These findings show that cyclophosphamide treatment decreases the development of diabetes by inhibiting the development of insulitis. This inhibitory action of cyclophosphamide on the diabetic process seems to be mediated by the induction of immunoregulatory cell activity. The suppression of cytokines that promote Th1 cell differentiation by cyclophosphamide treatment could also play a part in the diabetes sparing effect of cyclophosphamide. [Diabetologia (2000) 43: 986-994] Springer-Verlag Berlin Heidelberg, 2000 KeywordsBB rat nationallicence Cytokines nationallicence Cyclophosphamide nationallicence Immunoregulatory cell nationallicence Sobel D. O. Georgetown University School of Medicine, Washington, District of Columbia, USA, US aut Ahvazi B. Georgetown University School of Medicine, Washington, District of Columbia, USA, US aut Jun H.-S Julie McFarlane Diabetes Research Center, University of Calgary, Canada, CA aut Chung Y.-H Julie McFarlane Diabetes Research Center, University of Calgary, Canada, CA aut Yoon J.-W Julie McFarlane Diabetes Research Center, University of Calgary, Canada, CA aut https://doi.org/10.1007/s001250051480 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051480 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sobel D. O. Georgetown University School of Medicine, Washington, District of Columbia, USA, US aut NATIONALLICENCE 700 1- Ahvazi B. Georgetown University School of Medicine, Washington, District of Columbia, USA, US aut NATIONALLICENCE 700 1- Jun H.-S Julie McFarlane Diabetes Research Center, University of Calgary, Canada, CA aut NATIONALLICENCE 700 1- Chung Y.-H Julie McFarlane Diabetes Research Center, University of Calgary, Canada, CA aut NATIONALLICENCE 700 1- Yoon J.-W Julie McFarlane Diabetes Research Center, University of Calgary, Canada, CA aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer