Interaction between serum amyloid A and leukocytes - a possible role in the progression of vascular complications in diabetes.

Diabetes mellitus is associated with an increased incidence of cardiovascular events and microvascular complications. Serum amyloid A (SAA), a HDL apolipoprotein is a risk marker for cardiovascular disease. A permanent increase in SAA plasma levels is observed in diabetics. Because SAA acts on leukocytes, we evaluated whether the synthesis of proinflammatory cytokines and migration of neutrophils and monocytes induced by SAA is affected in diabetics. Cells, isolated from human blood, were cultured in the presence of SAA. TNF-alpha, IL-1beta, IL-8 and IL-1ra levels were measured by ELISA in the culture supernatants and in serum of subjects. Neutrophils and monocytes migration were followed in a chemotaxis chamber. We make the novel observation that neutrophils and monocytes of diabetics are more responsive to SAA for the induction of the proinflammatory cytokine IL-1beta and the proangiogenic and chemotactic protein IL-8. Incremental TNF-alpha production was also found to occur when monocytes were stimulated with SAA. Cell migration was also increased. The increased production of cytokines and increased migration of leukocytes from diabetics in response to SAA may contribute to a sustained accumulation and activation of inflammatory cells in the disease. Accordingly, the hyper-responsiveness of leukocytes to SAA may be relevant to the proinflammatory conditions associated to vascular complications in diabetic patients.