Anne Sofie Andreasen Theis Pedersen-Skovsgaard Ronan M. G. Berg Kira Dynnes Svendsen Bo Feldt-Rasmussen Bente K. Pedersen Kirsten Møller Type 2 diabetes mellitus is associated with impaired cytokine response and adhesion molecule expression in human endotoxemia Received: 17 July 2009 Accepted: 1 December 2009 Published online: 13 March 2010 Ó Copyright jointly held by Springer and ESICM 2010 A. S. Andreasen ( ) ) Á T. Pedersen-Skovsgaard Á R. M. G. Berg Á B. K. Pedersen Á K. Møller Centre of Inflammation and Metabolism, Department of Infectious Diseases, University Hospital Rigshospitalet, Rigshospitalet-M 7641, Blegdamsvej 9, 2100 Copenhagen, Denmark e-mail: sofie_andreasen@msn.com Tel.: ?45-35-457545 Fax: ?45-35-457644 A. S. Andreasen Á K. Møller Intensive Care Unit 4131, University Hospital Rigshospitalet, Copenhagen, Denmark K. D. Svendsen Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark B. Feldt-Rasmussen Department of Nephrology, University Hospital Rigshospitalet, Copenhagen, Denmark Abstract Purpose: Type 2 diabe- tes is associated with an increased risk of acquiring infectious diseases and developing sepsis. This may partly be due to immune dysfunction. We investigated the in vivo innate immune response of type 2 diabetic persons to an intravenous injection of E. coli lipopolysaccharide (LPS). Methods: After ethics approval, informed consent and a thorough physical examination, 19 type 2 dia- betic patients and 23 healthy controls were included. LPS was given as an intravenous bolus injection of 0.3 ng/ kg. Physiological variables, white blood cell count, and plasma con- centrations of tumour necrosis factor (TNF), interleukin-6 (IL-6), interleu- kin-1 receptor antagonist (IL-1ra), and the adhesion molecules E-selec- tin, vascular adhesion molecule (VCAM)-1, and intracellular adhe- sion molecule (ICAM)-1 were measured hourly for 8 h. Results: LPS injection induced a systemic inflammatory response with increases in neutrophils, temperature, heart rate and plasma concentrations of cytokines and adhesion molecules in healthy and type 2 diabetic volun- teers. Type 2 diabetes was associated with less pronounced LPS-induced increases in TNF, IL-1ra, VCAM-1 and ICAM-1. There was a trend towards an attenuated upregulation of E-selectin in diabetics, even though the plasma concentration tended to be generally higher compared to healthy controls. Conclusions: Patients with type 2 diabetes exhibit an attenuated increase in plasma levels of TNF and IL-1ra, as well as an attenuated upregulation of VCAM-1 and ICAM- 1 to LPS in vivo. This finding may provide a mechanistic explanation for the adverse outcome seen during infectious diseases in diabetic patients. Keywords Type 2 diabetes Á Sepsis Á Inflammation Á LPS Á Cytokines Á Adhesion molecules Introduction Type 2 diabetes mellitus (T2DM) is associated with an increased risk of developing infectious diseases and sep- sis, and the overall mortality due to infections is nearly twice as high when compared to nondiabetic patients [1]. This risk may be related to dysregulated humoral and cellular responses to infectious agents [2]. Thus, ex vivo studies on immune cells from persons with T2DM have shown pronounced, as well as attenuated, cytokine responses to lipopolysaccharide (LPS) stimulation when compared to cells from nondiabetic persons [3–5]. In addition, impaired chemotaxis and phagocytic capacity have been found in neutrophils and monocytes from Intensive Care Med (2010) 36:1548–1555 DOI 10.1007/s00134-010-1845-1 ORIGINAL