Increased secretion of TGF-beta 1 by peripheral blood mononuclear cells from patients with Type 1 diabetes mellitus with diabetic nephropathy

Aims To study transforming growth factor (TGF)-beta1 secretion by periphera l blood mononuclear cells (PBMC) from Type 1 diabetic patients with and wit hout nephropathy. Methods Thirty normoalbuminuric Type 1 diabetic patients (urinary albumin e xcretion rate (AER) < 20 <mu>g/min), 12 microalbuminuric (AER 20-200 mug/ m in), 10 nephropathic (AER > 200 mug/min), and 13 non-diabetic individuals w ere recruited. TGF-beta1 secretion by PBMC was measured by enzyme immunoass ay (EIA) after 48 h culture with and without phytohaemagglutinin (PHA) (5 m ug/ml). Results After 48 h culture, the highest TGF-beta1 levels secreted by unstim ulated PBMC were found in patients with nephropathy (median 6.2 (range 0.9- 20.0) ng/ml) when compared to patients with normal albumin excretion 14.1 ( 0.2-11.3) ng/ml), microalbuminuria (1.8 (0.2-6.4) ng/ml) and healthy contro ls (1.0 (0.2-7.0) ng/ml);P = 0.02 for the three diabetic groups and P = 0.0 06 for all groups. At 48 h, the PHA-stimulated TGF-beta1 levels were 12.4 ( 2.9-30.0) ng/ml in nephropathic, 7.3 (0.5-21.2) ng/ml in normoalbuminuric, and 5.5 (0.5-27.6) ng/ml in microalbuminuric patients (P = 0.05). A correla tion was observed between TGF-beta1 and diastolic blood pressure in the sub group of patients with incipient and overt nephropathy (r = 0.45, P = 0.04) . Conclusions Type 1 diabetic patients with overt nephropathy show increased TGF-beta1 secretion by PBMC. Diastolic blood pressure levels correlated wit h TGF-beta1 secretion in diabetic patients with nephropathy. Increased TGF- beta1 secretion by PBMC may be associated with renal and vascular disease i n Type I diabetes mellitus.