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J Thorac Cardiovasc Surg 2003;126:718-725
© 2003 The American Association for Thoracic Surgery

Surgery for congenital heart disease

Plasma levels of interleukin-8 and expression of interleukin-8 receptors on circulating neutrophils and monocytes after cardiopulmonary bypass in children

^a University Children’s Hospital, Zurich, Switzerland
^b University Children’s Hospital, Berne, Switzerland
^c Department of Cardiovascular Surgery, University Hospital, Berne, Switzerland
^d Institute of Immunology, University of Berne, Berne, Switzerland

Received for publication October 8, 2002; revisions received November 25, 2002; revisions received December 3, 2002; accepted for publication January 10, 2003.

^* Address for reprints: Peter Gessler, MD, University Children’s Hospital, Steinwiesstr. 75, CH 8032, Zurich, Switzerland
peter.gessler{at}kispi.unizh.ch

OBJECTIVE: Cardiopulmonary bypass induces a systemic inflammatory response that causes substantial clinical morbidity. This study sought to determine cellular and humoral variables of inflammation. We hypothesized that chemokines are a major source of stimulation of neutrophils and monocytes in pediatric cardiac surgery.

METHODS: We performed an observational prospective clinical study of 20 pediatric patients before and after cardiopulmonary bypass. Plasma levels of interleukin-6, interleukin-8, myeloperoxidase, and nitric oxide were measured by immunoassays. Expression of interleukin-8 receptors (CXCR1, CXCR2) and CD14 of circulating neutrophils and monocytes was assessed by flow cytometry. Clinical evaluations included length of inotropic support and mechanical ventilation as well as oxygenation.

RESULTS: Two hours after cardiopulmonary bypass, plasma levels of interleukin-6 and interleukin-8 were strongly increased (P = .0001 and P = .0032, respectively). Interleukin-6 and interleukin-8 concentrations correlated with the length of inotropic support, as well as with the length of mechanical ventilation (r > .70, P .0006), and were inversely related to the ratio of arterial oxygen tension to fraction of inspired oxygen. There was a strong association between the postoperative levels of interleukin-6 and nitric oxide, as well as between interleukin-6 and CD14 expression on monocytes (r > .62, P .0031). The expression of CXCR2 but not CXCR1 on neutrophils and monocytes correlated negatively with the levels of interleukin-8 and myeloperoxidase.

CONCLUSIONS: After cardiopulmonary bypass, impairment of cardiovascular and respiratory function correlated with the levels of interleukin-6 and interleukin-8 as mediators of an inflammatory response. The negative correlation of CXCR2 expression with interleukin-8 and myeloperoxidase indicates that myeloid cells were stimulated by CXC chemokines with Glu-Leu-Arg (ELR) motif and thereby contributed to tissue damage, leading to impairment of cardiovascular and respiratory function.

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