Beneficial effects of troglitazone on neutrophil dysfunction in multiple low-dose streptozotocin-induced diabetic mice
Open Access
- 16 June 2004
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 137 (2) , 263-271
- https://doi.org/10.1111/j.1365-2249.2004.02532.x
Abstract
Patients with poorly controlled diabetes are at high risk of acquiring bacterial infections. However, conflicting results have been reported on neutrophil function in diabetes. We periodically evaluated neutrophil dysfunction in multiple low‐dose streptozotocin (STZ)‐induced diabetic mice, and then evaluated the effects of troglitazone and other thiazolidinediones (TZDs) on the decline of neutrophil function. Zymosan was injected intraperitoneally and neutrophil infiltration and phagocytosis were evaluated. While phagocytosis of zymosan by peritoneal neutrophils was consistently reduced in diabetic mice, neutrophil infiltration was decreased on day 30, but increased on day 40 after STZ injection. The in vitro chemotactic and phagocytic activities of blood neutrophils in mice that did not receive zymosan were consistently reduced in diabetic mice. Phorbol myristate acetate (PMA)‐stimulated superoxide production by zymosan‐induced peritoneal neutrophils and the levels of zymosan‐induced tumour necrosis factor (TNF)‐α and interleukin (IL)‐1β in peritoneal exudate fluids were also reduced in the diabetic mice. Treatment of the diabetic mice with troglitazone beginning 2 weeks after STZ injection did not improve hyperglycaemia but did prevent the decline of zymosan‐induced neutrophil infiltration on day 30, and additionally promoted the increased infiltration on day 40. Troglitazone also promoted the chemotactic activity of blood neutrophils isolated from normal mice in vitro. Rosiglitazone but not pioglitazone induced a similar effect. Neutrophil phagocytosis was not enhanced by troglitazone either in vivo or in vitro. Taken together, neutrophil function is impaired by STZ‐induced diabetes, but inflammatory infiltration does not always vary with the chemotactic disability or cytokine levels. Furthermore, troglitazone and rosiglitazone were suggested to improve at least neutrophil chemotactic activity in these animals.Keywords
This publication has 58 references indexed in Scilit:
- Dual Function of Troglitazone in ICAM-1 Gene Expression in Human Vascular EndotheliumBiochemical and Biophysical Research Communications, 2001
- Activation of Human Peroxisome Proliferator-Activated Receptor (PPAR) Subtypes by PioglitazoneBiochemical and Biophysical Research Communications, 2000
- Troglitazone and related compoundsLife Sciences, 2000
- Peroxisome Proliferator–Activated Receptor-γ Ligands Inhibit Nitric Oxide Synthesis in Vascular Smooth Muscle CellsHypertension, 2000
- Inhibition by troglitazone of the antigen‐induced production of leukotrienes in immunoglobulin E‐sensitized RBL‐2H3 cellsBritish Journal of Pharmacology, 2000
- Troglitazone Has a Scavenging Effect on Reactive Oxygen SpeciesBiochemical and Biophysical Research Communications, 1997
- Measurement and drug induced modulation of interleukin-1 level during zymosan peritonitis in miceInflammation Research, 1995
- Production of superoxide anion by polymorphonuclear leukocytes from diabetic patients with or without diabetic retinopathyDocumenta Ophthalmologica, 1995
- Evidence that endogenous interleukin-1 is involved in leukocyte migration in acute experimental inflammation in rats and miceInflammation Research, 1992
- Defective phagocytosis in insulin controlled diabetics: evidence for a reaction between glucose and opsonising proteins.Journal of Clinical Pathology, 1984