Altered cytokine and nitric oxide secretion in vitro by macrophages from diabetic type II-like db/db mice

Macrophage dysfunction is a likely mechanism underlying common diabetic com plications such as increased susceptibility to infection, accelerated ather osclerosis, and disturbed wound healing. There are no available studies on the function of tissue macrophages in diabetes in humans. We have therefore studied peritoneal macrophages from diabetic type 2-like db/db mice. We fo und that the release of tumor necrosis factor-alpha and interleukin-1 beta from lipopolysaccharide plus interferon-gamma-stimulated macrophages and va scular endothelial. growth factor from both stimulated and nonstimulated ma crophages was significantly reduced in diabetic animals compared with nondi abetic controls. Nitric oxide production from the stimulated db/db macropha ges was significantly higher than that in the db/+ cultures, whereas there was no difference in their ability to generate reactive oxygen species. Whe n studied both at light and electron microscopic levels, macrophages in dia betic animals had an altered morphological appearance compared with those o f normal controls. We conclude that the function and morphology of the macr ophages are disturbed in db/db mice and that this disturbance is related to the mechanisms underlying common inflammatory and degenerative manifestati ons in diabetes.