Sustained elevation of the proinflammatory cytokine IL-6 but not CRP in serum of type 2 diabetes patients with diabetic foot syndrome

B. Rose; D. I. Shin; G. Friese; T. Othman; U. Poschen; C. Herder; W. A. Scherbaum; W. Koenig; S. Martin

doi:10.1055/s-2006-933075

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Sustained elevation of the proinflammatory cytokine IL-6 but not CRP in serum of type 2 diabetes patients with diabetic foot syndrome

B Rose ¹, DI Shin ¹, G Friese ¹, T Othman ¹, U Poschen ¹, C Herder ¹, WA Scherbaum ¹, W Koenig ², S Martin ¹

¹German Diabetes Center, German Diabetes Clinic, Duesseldorf, Germany
²University of Ulm Medical Center, Department of Internal Medicine II-Cardiology, Ulm, Germany

Abstract

Objectives: The development of a diabetic foot syndrome (DFS) is a common complication of diabetes accompanied by strong impairments of life quality. An association with immunological processes has not been described yet. Therefore, we analysed serum levels of immune parameters in type 2 diabetes (T2D) patients with and without DFS.

Methods: 39 patients (14 women, 25 men) with T2D and active foot ulcers (classified according to Wagner) and 110 T2D patients (49 women, 61 men) without history of previous foot lesions were analysed. Blood samples were drawn at hospitalisation, after 7 and 14 days. Serum was analysed for the acute phase protein CRP by high sensitivity latex enhanced nephelometric assay and for the proinflammatory cytokine interleukin-6 (IL-6) using high sensitive ELISA. Patients were intensively evaluated for clinical parameters including wound size, infection grade and diabetes-related complications.

Results: At hospitalisation, patients with DFS exhibited significantly elevated levels of IL-6 and CRP compared to controls (median 10.2 pg/ml vs. 3.8 pg/ml, p<0.0001 for IL-6 and 11.0mg/l vs. 2.6mg/l for CRP, p<0.0001). Whereas CRP levels declined during the first 14 days of intensive therapy along with clinical signs of infection, IL-6 levels persisted during the observation period (10.2 pg/ml vs. 8.6 pg/ml at day 14; ns). For both, IL-6 and CRP, a strong correlation with severity of foot ulcer (r=0.50, p<0.01 for IL-6, r=0.55, p<0.001 for CRP) and duration of hospitalisation was observed. Interestingly, CRP but not IL-6 was associated with the grade of infection of foot ulcer (r=0.34, p<0.05 for CRP).

Conclusion: Elevated serum levels of IL-6 and CRP were observed in type 2 diabetes patients with DFS compared to patients without DFS. IL-6, but not CRP levels persisted independently of clinical outcome and adequate antiinfective therapy. Additionally, patients with severe ulcers exhibited a stronger immune activation. These results suggest a role of innate immunity in the pathogenesis of diabetic foot syndrome independent of acute phase response.