Regulated upon activation, normal T-cell expressed and secreted chemokine and interleukin-6 in rheumatic pulmonary hypertension, targets for therapeutic decisions

Eur J Cardiothorac Surg. 2010 Apr;37(4):853-8. doi: 10.1016/j.ejcts.2009.10.010. Epub 2009 Nov 20.

Abstract

Background: Recent studies have highlighted the possible influence of chemokines and cytokines on several types of pulmonary arterial hypertension (PAH). Increasing interest has also been focussed on their role as a cause of post-cardiopulmonary bypass (CPB) organ dysfunction.

Hypothesis: Chemokines and cytokines are involved in the pathobiology of rheumatic PAH.

Methods: Serum levels of the chemokine, regulated upon activation, normal T-cell expressed and secreted (RANTES) and the cytokine interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) in 35 patients with rheumatic mitral valve disease and 10 matched healthy subjects (control group). Eleven patients (31.4%) had severe pulmonary hypertension. Subsequently, 23 patients underwent mitral valve replacement. The relation of RANTES and IL-6 circulating level with postoperative organ dysfunction was analysed through multiple organ dysfunction score (MODS).

Results: Patients with severe PAH have a significantly higher mean serum level of RANTES compared with other patients (6138.6+/-3543.8 pg/ml vs 1818.2+/-475.2 pg/ml, p=0.0003). The serum level of IL-6 in the patients was statistically different from that of the control (378+/-50.8 pg/ml vs 262+/-90.5 pg/ml, respectively, p=0.002). Patients who required postoperative inotropes had higher preoperative and post-CPB levels of both RANTES and IL-6. While patients with postoperative lung dysfunction had higher levels of IL-6 preoperatively and post-CPB and lower levels of RANTES post-CPB.

Conclusions: RANTES and IL-6 should be investigated as potential therapeutic targets in the control of rheumatic PAH. Improved understanding of the contribution of RANTES and IL-6 to adverse postoperative complications can lead to improved patient outcome.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Chemokine CCL5 / blood*
  • Female
  • Heart Valve Prosthesis Implantation / adverse effects
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / immunology*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Mitral Valve Insufficiency / complications
  • Mitral Valve Insufficiency / immunology
  • Mitral Valve Insufficiency / surgery
  • Mitral Valve Stenosis / complications
  • Mitral Valve Stenosis / immunology
  • Mitral Valve Stenosis / surgery
  • Multiple Organ Failure / etiology
  • Multiple Organ Failure / immunology
  • Prospective Studies
  • Rheumatic Heart Disease / complications
  • Rheumatic Heart Disease / immunology*
  • Rheumatic Heart Disease / surgery
  • Young Adult

Substances

  • Biomarkers
  • CCL5 protein, human
  • Chemokine CCL5
  • Interleukin-6