Systemic biomarkers of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis

Abstract

Background: The purpose of this study was to investigate mediators of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis (CNPA), a locally, destructive process of the lung due to invasion by Aspergillus species.

Methods: Measurements of selected biomarkers in 10 patients with CNPA and 19 healthy, matched controls were performed with enzyme-linked immunosorbent assay (ELISA) and multiplex methodology. The gene expressions of relevant biomarkers were analyzed with real-time quantitative RT-PCR.

Results: Increased concentrations of circulating mediators of inflammation interleukin (IL)-6, IL-8, RANTES, TNF-α, ICAM-1 and mediators involved in endothelial activation and thrombosis (vWF, TF and PAI-1) were observed in patients with CNPA. The concentration of the anti-inflammatory cytokine IL-10 was increased both in plasma and in PBMC in the patient population. The gene expression of CD40L was decreased in PBMC from the patient group, accompanied by decreased concentrations of soluble (s) CD40L in the circulation.

Conclusions: The proinflammatory response against Aspergillus may be counteracted by reduced CD40L and sCD40L, as well as increased IL-10, which may compromise the immune response against Aspergillus in patients with CNPA.

Figure 1

Plasma and serum levels of IL-6, IL-10, IL-8, RANTES, TNF-α, ICAM-1, soluble CD40L, vWF, tissue factor (TF), and PAI-1 in patients with CNPA (n = 10, black columns) and healthy controls (n = 19, white columns). Data are mean ± SEM. P- values are adjusted for the use of voriconazole. *p < 0.05, **p < 0.01 and ***p < 0.001 versus controls.

Figure 2

mRNA expression of IL-6, PAI-1, RANTES, IL-10, IL-8, TNF-a, ICAM-1, CD40, and CD40L in 9 patients with CNPA and 10 healthy controls as assessed by real-time quantitative RT-PCR. Data are mean ± SEM in relation to the control gene β-actin and healthy controls are normalized equal to 1. *p < 0.05 and **p < 0.01 versus controls.