interleukin-8 and Malaria--Vivax

Cytokines and chemokines are immune response molecules that display diverse functions, such as inflammation and immune regulation. In Plasmodium vivax infections, the uncontrolled production of these molecules is thought to contribute to pathogenesis and has been proposed as a possible predictor for disease complications. The objective of this study was to evaluate the cytokine profile of P. vivax malaria patients with different clinical outcomes to identify possible immune biomarkers for severe P. vivax malaria. The study included patients with non-severe (n = 56), or severe (n = 50) P. vivax malaria and healthy controls (n = 50). Patient plasma concentrations of IL-4, IL-2, CXCL10, IL-1β, TNF-α, CCL2, IL-17A, IL-6, IL-10, IFN-γ, IL-12p70, CXCL8 and active TGF-β1 were determined through flow cytometry. The levels of several cytokines and chemokines, CXCL10, IL-10, IL-6, IL-4, CCL2 and IFN-γ were found to be significantly higher in severe, compared to non-severe P. vivax malaria patients. Severe thrombocytopenia was positively correlated with IL-4, CXCL10, IL-6, IL-10 and IFN-γ levels, renal dysfunction was related to an increase in IL-2, IL-1β, IL-17A and IL-8, and hepatic impairment with CXCL10, MCP-1, IL-6 and IFN-γ. A Lasso regression model suggests that IL-4, IL-10, CCL2 and TGF-β might be developed as biomarkers for severity in P. vivax malaria. Severe P. vivax malaria patients present specific cytokine and chemokine profiles that are different from non-severe patients and that could potentially be developed as biomarkers for disease severity.

Topics: Biomarkers; Chemokine CCL2; Chemokines; Cytokines; Humans; Interleukin-10; Interleukin-17; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Malaria; Malaria, Vivax; Plasmodium vivax; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

Topics: Acute Disease; Adult; Brazil; Case-Control Studies; Chemokine CCL4; Chemokines; Convalescence; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Hematocrit; Humans; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-17; Interleukin-1beta; Interleukin-4; Interleukin-6; Interleukin-8; Malaria, Falciparum; Malaria, Vivax; Male; Parasitemia; Plasmodium falciparum; Plasmodium vivax; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

The Duffy antigen/receptor for chemokines (DARC), first identified on erythrocytes, functions not only as a promiscuous chemokine receptor but also as a receptor for the malarial parasite, Plasmodium vivax. The recent finding that DARC is ubiquitously expressed by endothelial cells lining postcapillary venules provides a possible insight into the function of this receptor because this anatomic site is an active interface for leukocyte trafficking. However, the biological significance of DARC is questionable since it has not yet been determined whether individuals lacking the expression of this protein on their erythrocytes (Duffy negative individuals), who are apparently immunologically normal, express the receptor on endothelial cells. However, we report here that DARC is indeed expressed in endothelial cells lining postcapillary venules and splenic sinusoids in individuals who lack the erythrocyte receptor. These findings are based on immunohistochemical, biochemical, and molecular biological analysis of tissues from Duffy negative individuals. We also present data showing that, in contrast to erythrocyte DARC, cells transfected with DARC internalize radiolabeled ligand. We conclude that the DARC may play a critical role in mediating the effects of proinflammatory chemokines on the interactions between leukocyte and endothelial cells since the molecular pathology of the Duffy negative genotype maintains expression on the latter cell type.

Topics: Amino Acid Sequence; Antigens, Protozoan; Base Sequence; Carrier Proteins; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Duffy Blood-Group System; Endocytosis; Endothelium, Vascular; Erythrocyte Membrane; Gene Expression; Genes; Genetic Predisposition to Disease; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Malaria, Vivax; Molecular Sequence Data; Polymerase Chain Reaction; Protozoan Proteins; Receptors, Cell Surface; Recombinant Fusion Proteins; Transfection; Tumor Cells, Cultured; Veins