Beneficial effects of troglitazone on neutrophil dysfunction in multiple low-dose streptozotocin-induced diabetic...

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)-alpha and interleukin (IL)-1beta 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.