title: Timing of pentoxifylline treatment determines its protective effect on diabetes development in the Bio Breeding rat.
abstract: Diabetes-prone Bio Breeding (DP-BB) rats spontaneously develop diabetes between 60 and 120 days of age. Diabetes-resistant (DR)-BB rats can be induced to develop diabetes by poly(I:C) and anti-RT6. Here, we studied the effect of pentoxifylline, a potent anti-inflammatory agent, on diabetes development in both BB rat models of insulin-dependent diabetes mellitus and investigated whether these effects were related to differential modulation of tumour necrosis factor (TNF)-alpha and interleukin-10. When DP-BB rats received pentoxifylline from day 60 onwards, diabetes development was delayed and reduced. The other treatment protocols had no effect. In DR-BB rats, pentoxifylline treatment resulted only in a delay of diabetes development. In both BB rat models, in vivo pentoxifylline treatment potently suppressed TNF-alpha, but only moderately affected interleukin-10 production in vitro. These results show that timing of pentoxifylline treatment determines its protective effect on diabetes development in DP-BB rats. The observed pentoxifylline-induced increase of the interleukin-10/TNF-alpha ratio might be a mechanism for protection or delay of the diabetes development.
authors.affiliation: Department of Cell Biology, Immunology Section, Faculty Medical Sciences, Groningen University, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Visser
authors.forename: Herman
authors.initials: H
authors.lastname: Groen
authors.forename: Flip
authors.initials: F
authors.lastname: Klatter
authors.forename: Jan
authors.initials: J
authors.lastname: Rozing
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D010431:Pentoxifylline / Q000627:therapeutic use*; D051381:Rats; D011913:Rats, Inbred BB; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010431:Pentoxifylline