Serum Cytokines in Young Pediatric Patients with Congenital Cardiac Shunts and Altered Pulmonary Hemodynamics

Abstract

Background and Objective. Inflammation is central in the pathogenesis of pulmonary hypertension. We investigated how serum cytokines correlate with clinical features, hemodynamics, and lung histology in young patients with pulmonary hypertension associated with congenital cardiac shunts. Design. Prospective, observational study. Methods and Results. Patients (n = 44) were aged 2.6 to 37.6 months. Group I patients (n = 31) were characterized by pulmonary congestion and higher pulmonary blood flow compared to group II (p = 0.022), with no need for preoperative cardiac catheterization. Group II patients (n = 13) had no congestive features. At catheterization, they had elevated pulmonary vascular resistance (5.7 [4.4–7.4] Wood units·m2, geometric mean with 95% CI). Cytokines were measured by chemiluminescence. Macrophage migration inhibitory factor (MIF) was found to be inversely related to pulmonary blood flow (r = −0.33, p = 0.026) and was higher in group II (high pulmonary vascular resistance) compared to group I (high pulmonary blood flow) (p = 0.017). In contrast, RANTES chemokine (regulated on activation, normal T cell expressed and secreted) was characteristically elevated in Group I (p = 0.022). Interleukin 16 was also negatively related to pulmonary blood flow (r S = −0.33, p = 0.029) and was higher in patients with obstructive vasculopathy at intraoperative lung biopsy (p = 0.021). Conclusion. Cytokines seem to be important and differentially regulated in subpopulations of young patients with cardiac shunts.

Accelerated Cardiac Aging in Patients With Congenital Heart Disease

“…Inflammatory cells and cytokines have been shown to be activated in the pulmonary microvasculature of patients with communications between cardiac chambers or the great arteries leading to increased pulmonary blood flow and pressure. A differential pattern of cytokines was described in children with high pulmonary vascular resistance compared to children with high pulmonary blood flow, with the first group showing higher levels of Macrophage migration inhibitory factor (MIF) and Interleukin 16 ( 124 ).…”

Relation of Macrophage Migration Inhibitory Factor to Pulmonary Hemodynamics and Vascular Structure and Carbamyl-Phosphate Synthetase I Genetic Variations in Pediatric Patients with Congenital Cardiac Shunts

“…It is also associated with the exaggerated recruitment of peripheral blood mononuclear cells and proinflammatory endothelial cell behavior [1, 7–9]. In a recent study of ours involving pediatric patients with congenital cardiac communications, heightened serum MIF was observed in a specific subgroup of subjects with elevated pulmonary vascular resistance [10]. This finding suggests the possible involvement of this chemokine in the early development of pulmonary vasculopathy in congenital heart disease.…”

Multiple roles of macrophage migration inhibitory factor in pulmonary hypertension

“…PH is a common complication in newborn infants with CDH, in addition to lung hypoplasia. The vascular defects associated with PH, which are characterized by increased muscularization of the arterioles and capillaries, start to develop early in gestation (67). MIF expression has been shown to be 10-fold higher in newborns than in children and adults (50).…”