Type I immune response cytokine-chemokine cascade is associated with pulmonary arterial hypertension.

Abstract

BACKGROUND:

Perivascular infiltrating mononuclear cells have been described in the vasculopathy found in multiple types of pulmonary arterial hypertension (PAH). We determined the expression of a specific type 1 immune response cytokine-chemokine cascade-interleukin (IL)-18 → (monokine induced by γ-interferon [MIG]/chemokine [C-X-C motif] ligand [CXCL] 9, interferon γ-induced protein [IP]-10/CXCL10 and interferon-inducible T-cell α chemoattractant [ITAC]/CXCL11)-in plasma samples from individuals with World Health Organization (WHO) Group 1 PAH.

METHODS:

We analyzed cytokine and chemokine protein levels in plasma from 43 individuals with WHO Group 1 PAH by enzyme-linked immunosorbent assay compared with 35 healthy individuals. Immunohistochemical studies on tissue specimens from WHO Group 1 PAH patients were performed for cytokines and chemokines and their respective receptors.

RESULTS:

Plasma IL-18 levels from WHO Group 1 PAH patients were significantly increased compared with healthy controls. Downstream chemokine CXCL10, but not CXCL9 or CXCL11, was markedly elevated compared with controls. Cellular sources of IL-18 were medial but not intimal smooth muscle cells. IL-18Rα was expressed from medial smooth muscle cells, endothelial cells, and mononuclear cells. CXCL10 and its main receptor, CXCR3, were expressed from infiltrating vascular wall mononuclear cells.

CONCLUSIONS:

These data suggest that augmented expression of IL-18 and CXCL10 may perpetuate an inflammatory milieu that eventually contributes to the vascular obstruction characteristic of PAH.

• Authors: David J Ross, Robert M Strieter, Michael C Fishbein, Abbas Ardehali, John A Belperio
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 31 Issue 8 Pg. 865-73 (Aug 2012) ISSN: 1557-3117 [Electronic] United States
• PMID: 22658713 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• CXCR3 protein, human
• Chemokine CXCL10
• Chemokines
• Cytokines
• Interleukin-18
• Receptors, CXCR3
• Receptors, Interleukin-18

Topics

• Case-Control Studies
• Chemokine CXCL10 (metabolism)
• Chemokines (metabolism)
• Cytokines (metabolism)
• Endothelium, Vascular (metabolism)
• Humans
• Hypertension, Pulmonary (classification, immunology, metabolism)
• Immunity, Innate (physiology)
• Interleukin-18 (metabolism)
• Leukocytes, Mononuclear (metabolism)
• Muscle, Smooth, Vascular (metabolism)
• Receptors, CXCR3 (metabolism)
• Receptors, Interleukin-18 (metabolism)
• World Health Organization