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

Abstract

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. 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. 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. 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.