Cytokines, endothelial activation and microvascular dysfunction in acute respiratory syndrome due to Plasmodium vivax

Abstract

Plasmodium vivax, previously considered benign, is now recognized as capable of causing severe disease syndromes associated with fatal outcomes. Endothelial activation is associated with circulating parasites, and systemic inflammation may contribute to pathology in vivax malaria. Microvascular dysfunction likely contributes to impaired tissue perfusion. Severe vivax malaria due to acute lung injury/acute respiratory distress syndrome (ARDS) may be linked to microvascular dysfunction in that organ. We carried out a study of vivax malaria patients with uncomplicated infection or ARDS as cases and compared them to healthy controls. Fifty vivax malaria patients (microscopy confirmed) were classified as having uncomplicated infection (n = 25) or severe malaria due to ARDS (n = 25) applying the standard WHO definition of sever malaria. Healthy controls (n = 50) participated in this study voluntarily with no history of malaria. Concentrations of cytokines, TNF- α,IL-6, IL-10 and endothelial activation markers ICAM-1 (intracellular adhesion molecule-1),VCAM- 1(vascular adhesion molecule-1) and E-selectin were determined by enzyme-linked immunosorbant assay (ELISA).Correlation of cytokines and endothelial activation markers was done using Pearson two way correlation matrix. The significance of biomarkers as indicators of disease severity was examined by multi-variate analyses. Cytokines levels in all vivax malaria cases were compared with healthy controls and found to be significantly elevated. Healthy Vs uncomplicated P.vivax malaria, Selectin (9809 vs. 41622 pg/ml, p = 0.0001), ICAM (1089 vs. 255 pg/ml, p = 0.03), TNF (181 vs. 137 pg/ml, p = 0.3), IL6 (369 vs. 90 pg/ml, p = 0.001), IL10 (65 vs. 1001 pg/ml, p = 0.003) compared to healthy controls. Biomarkers levels in uncomplicated vs Pv- ARDS; E-Selectin (4162 vs. 66043 pg/ml, p = 0.03), ICAM (1089vs. 1895 pg/ml, p = 0.03), TNF (181vs. 520 pg/ml, p = 0.001), IL10 (1001 vs. 4753 pg/ml, p = 0.003) levels were significantly higher in ARDS severe malaria case compare to uncomplicated case. Cytokine-mediated endothelial activation pathway is a possible mechanism of pathogenesis in severe P. vivax. Increase levels of IL-10 and TNF may be plausible biomarkers of ARDS in P. vivax infection. However, further studies are required to understand the relevance of cytokines in manifestations of ARDS in P. vivax malaria