Plasma cytokine profile in tropical endomyocardial fibrosis: predominance of TNF-a, IL-4 and IL-10

Abstract

Background: The participation of immune/inflammatory mechanisms in the pathogenesis of tropical endomyocardial fibrosis (EMF) has been suggested by the finding of early blood and myocardial eosinophilia. However, the inflammatory activation status of late-stage EMF patients is still unknown.

Methodology/principal findings: We evaluated pro- and anti-inflammatory cytokine levels in plasma samples from late stage EMF patients. Cytokine levels of Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-γ, Interleukin (IL)-2, IL-4, IL-6, and IL-10 were assayed in plasma samples from 27 EMF patients and compared with those of healthy control subjects. All EMF patients displayed detectable plasma levels of at least one of the cytokines tested. We found that TNF-α, IL-6, IL-4, and IL-10 were each detected in at least 74% of tested sera, and plasma levels of IL-10, IL-4, and TNF-α were significantly higher than those of controls. Plasma levels of such cytokines positively correlated with each other.

Conclusions/significance: The mixed pro- and anti-inflammatory/Th2circulating cytokine profile in EMF is consistent with the presence of a persistent inflammatory stimulus. On the other hand, the detection of increased levels of TNF-α may be secondary to the cardiovascular involvement observed in these patients, whereas IL-4 and IL-10 may have been upregulated as a homeostatic mechanism to buffer both production and deleterious cardiovascular effects of pro-inflammatory cytokines. Further studies might establish whether these findings play a role in disease pathogenesis.

Figure 1. Cytokine plasma levels of endomyocardial fibrosis patients and healthy subjects.

Dot plot represents cytokine levels (interleukin 2, 4, 6, 10, TNF-α and IFN-γ) from endomyocardial fibrosis patients (EMF) and healthy subjects (HS), evaluated by CBA. Horizontal lines indicate the median values. *Differences where P≤0.05 are indicated. (•Healthy Subjects;▪EMF patients).

Figure 2. Correlation among cytokine plasma levels of endomyocardial fibrosis patients.

Dot plots represent correlation between cytokine levels (interleukin 2, 4, 6, 10, TNF-α and IFN-γ) from endomyocardial fibrosis patients, evaluated by CBA.