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(Circulation. 2002;106:2608.)
© 2002 American Heart Association, Inc.

Basic Science Reports

CD14-Deficient Mice Are Protected Against Lipopolysaccharide-Induced Cardiac Inflammation and Left Ventricular Dysfunction

Pascal Knuefermann, MD; Shintaro Nemoto, MD, PhD; Arunima Misra, MD; Naoki Nozaki, MD; Gilberto Defreitas, BS; Sanna M. Goyert, PhD; Blase A. Carabello, MD; Douglas L. Mann, MD; Jesus G. Vallejo, MD

From the Department of Pediatrics, Section of Infectious Diseases (J.G.V.), and Department of Medicine (P.K., A.M., N.N., D.L.M., J.G.V.), Winters Center For Heart Failure Research, Veterans Affairs Medical Center (S.N., B.A.C.), Baylor College of Medicine, Houston, Tex; and North Shore University Hospital (S.M.G.), Manhasset, NY.

Correspondence to Jesus G. Vallejo, MD, Department of Pediatrics, Section of Infectious Diseases, One Baylor Plaza, Room 302A, Houston, TX 77030. E-mail jvallejo{at}bcm.tmc.edu

Background— The molecular mechanisms responsible for sepsis-induced myocardial dysfunction remain undefined. CD14 mediates the inflammatory response to lipopolysaccharide (LPS) in various organs including the heart. In this study we investigated the role of CD14 in LPS-induced myocardial dysfunction in vivo.

Methods and Results— Wild-type and CD14-deficient (CD14-D) mice were challenged with Escherichia coli LPS. Myocardial tumor necrosis factor, interleukin-1ß (IL-1ß), and NOS2 induction was measured before and 6 hours after LPS challenge. Echocardiographic parameters of left ventricular function were measured before and 6 hours after LPS administration. LPS challenge induced a significant increase in myocardial tumor necrosis factor and IL-1ß mRNA and protein expression in wild-type mice. In contrast, mRNA and protein levels for TNF and IL-1ß were significantly blunted in CD14-D mice. An increase in NOS2 protein was noted within 6 hours of LPS provocation only in the hearts of wild-type mice. This was associated with an increase in ventricular cGMP levels. Activation of nuclear factor-B was observed within 30 minutes of LPS in the hearts of wild-type mice but not in CD14-D mice. In wild-type mice, LPS significantly decreased left ventricular fractional shortening, velocity of circumferential shortening, and dP/dt_max. LPS-treated CD14-D mice maintained normal cardiac function.

Conclusions— These results suggest that CD14 is important in mediating the proinflammatory response induced by LPS in the heart and that CD14 is necessary for the development of left ventricular dysfunction during LPS-induced shock in vivo.

Key Words: immune system • shock • inflammation • echocardiography

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