interleukin-8 and Malaria

The interleukin 8 (IL-8)-receptor family includes two specific receptors (type A and B) that both bind IL-8 with high affinity. These receptors have been cloned, and belong to a superfamily of G-protein-linked receptors that signal in response to IL-8 on a variety of cell types. In contrast to these receptors, which have a narrow ligand-binding profile, a promiscuous IL-8 receptor has been found on human erythrocytes that binds a variety of chemokines with high affinity. This protein, known as the chemokine receptor, was recently shown to bind the malarial parasite Plasmodium vivax, and may play a major role in inflammation by limiting the concentration of soluble chemokines in the circulation.

Topics: Amino Acid Sequence; Animals; Antigens, Protozoan; Chemotactic Factors; Cytokines; Erythrocytes; Humans; Interleukin-8; Malaria; Molecular Sequence Data; Protozoan Proteins; Receptors, Cell Surface; Receptors, Interleukin; Receptors, Interleukin-8A; Signal Transduction

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

The immune status of women changes during and after pregnancy, differs between blood compartments at delivery and is affected by environmental factors particularly in tropical areas endemic for multiple infections. We quantified the plasma concentration of a set of thirty-one T

Topics: Adult; Brazil; Chemokines; Cohort Studies; Colombia; Cytokines; Female; Guatemala; Hepatocyte Growth Factor; Humans; Immunoglobulin G; India; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Malaria; Papua New Guinea; Placenta; Plasmodium; Pregnancy; Pregnancy Complications, Parasitic; Pregnant Women; Spain; Transforming Growth Factor beta

Amongst host genetic factors, cytokine gene polymorphism can be anticipated to be an important factor as qualitative, quantitative and time of secretion play an important role in disease outcome. We have investigated association of cytokine promoter SNPs with risk of Plasmodium falciparum malaria and disease severity in a case control study in malaria endemic Karbi Anglong district of Assam, India. Frequency of IL-8-251T/A (p=0.03 and p=0.01) and TGF-β1-509C/T (p=0.02 and p=0.03) was higher in malaria in comparison to control participants and non-malarial fever controls. Interestingly, a higher frequency of mutant allele of IL-10-819T/C was observed in non-malarial fever controls compared to malaria thus suggesting its role as a distinguishing marker of the two disease groups. Higher IL-8 expression and increased frequency of IL-8-251T/A in complicated malaria (p=0.002) was reported indicating its role in susceptibility to complicated malaria. In conclusion, our study suggests the role of mutant genotype of IL-8-251T/A as a marker of complicated malaria in our population. Surprisingly, decreased expression of TGF-β1 in uncomplicated malaria even in presence of high expressing mutant genotype was observed and needs to be investigated in context of the pool of activated cells producing the cytokine.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Child; Demography; Female; Fever; Gene Expression Regulation; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; India; Interleukin-8; Malaria; Male; Middle Aged; Polymorphism, Single Nucleotide; Transforming Growth Factor beta1; Young Adult

Pregnancy triggers immunological changes aimed to tolerate the fetus, but its impact on B lymphocytes is poorly understood. In addition, exposure to the Plasmodium parasite is associated with altered distribution of peripheral memory B cell (MBC) subsets. To study the combined impact of high malaria exposure and pregnancy in B cell subpopulations, we analyzed PBMCs from pregnant and nonpregnant individuals from a malaria-nonendemic country (Spain) and from a high malaria-endemic country (Papua New Guinea). In the malaria-naive cohorts, pregnancy was associated with a significant expansion of all switched (IgD(-)) MBC and a decrease of naive B cells. Malaria-exposed women had more atypical MBC and fewer marginal zone-like MBC, and their levels correlated with both Plasmodium vivax- and Plasmodium falciparum-specific plasma IgG levels. Classical but not atypical MBC were increased in P. falciparum infections. Moreover, active atypical MBC positively correlated with proinflammatory cytokine plasma concentrations and had lower surface IgG levels than the average. Decreased plasma eotaxin (CCL11) levels were associated with pregnancy and malaria exposure and also correlated with B cell subset frequencies. Additionally, active atypical and active classical MBC expressed higher levels of eotaxin receptor CCR3 than the other B cell subsets, suggesting a chemotactic effect of eotaxin on these B cell subsets. These findings are important to understand immunity to infections like malaria that result in negative outcomes for both the mother and the newborn and may have important implications on vaccine development.

Topics: Adult; Antibodies, Protozoan; Antigens, Protozoan; B-Lymphocyte Subsets; Chemokine CCL11; Female; Humans; Immunoglobulin D; Immunoglobulin G; Immunologic Memory; Interleukin-8; Lymphocyte Count; Malaria; Papua New Guinea; Plasmodium falciparum; Plasmodium vivax; Pregnancy; Receptors, CCR3; Spain

Topics: Animals; Duffy Blood-Group System; Filariasis; Filarioidea; Host-Parasite Interactions; Inflammation; Interleukin-8; Leukocytes; Macrophage Migration-Inhibitory Factors; Macrophages; Malaria; Receptors, Chemokine

Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three beta chemokines, macrophage-inflammatory protein 1 (MIP-1) alpha (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one alpha chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1 alpha and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1 beta and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.

Topics: Birth Weight; Cell Movement; Chemokine CCL1; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokines, CC; Female; Host-Parasite Interactions; Humans; Interleukin-8; Leukocyte Count; Macrophage Inflammatory Proteins; Malaria; Monocytes; Placenta; Pregnancy; Pregnancy Complications, Parasitic; RNA, Messenger

The present study revealed no changes in the serum levels of IL-8 in malaria patients compared with controls. Such result however, does not exclude a role for IL-8 in falciparum malaria, as it is produced by activated endothelial cells that may be captured by receptors on the endothelial surface. This would allow local concentrations of IL-8 to be generated at the vessel wall without being shed into the circulation. The marked elevation of ICAM-1 and VCAM-1 in serum of falciparum malaria patients may support the concept that dysfunction of the endothelium is important in the pathophysiology of the disease. Increased level of IL-6 in serum of patients may contribute to endothelial damage and dysfunction by expression of endothelial adhesion molecules that in turn result in infected erythrocytes attraction to the endothelium and pathologic endothelial dysfunction.

Topics: Biomarkers; Case-Control Studies; Cell Adhesion Molecules; Cytokines; Endothelium; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Malaria; Severity of Illness Index; Solubility; Vascular Cell Adhesion Molecule-1; Zambia

Topics: Acute Disease; Bacterial Infections; Chemotactic Factors; Chronic Disease; Granuloma; Humans; Immunity, Cellular; Interleukin-8; Malaria; T-Lymphocytes; Tuberculosis

The effect of treatment with interleukin-8 (IL-8), a neutrophil-activating cytokine, was investigated in normal and neutropenic mice infected with a lethal dose of Pseudomonas aeruginosa, Klebsiella pneumoniae, or Plasmodium berghei. Intraperitoneal (i.p.) IL-8 treatment was associated with accelerated death when IL-8 was administered shortly before i.p. infection with P. aeruginosa or shortly after i.p. infection with P. aeruginosa and K. pneumoniae. Histopathological analyses demonstrated a tendency to more severe organ lesions in IL-8-treated mice. Only nonneutropenic mice that received IL-8 shortly before the infectious challenge and at the site of infection were protected by IL-8. Whether IL-8 is protective of or detrimental to the survival of infection appeared to depend on the presence of bacteria at the injection site and on the presence of neutropenia. IL-8 may be an important participant in the cascade of interacting cytokines that is induced by the lethal infectious challenge.

Topics: Animals; Bacterial Infections; Brain; Female; Interleukin-8; Klebsiella Infections; Klebsiella pneumoniae; Leukocyte Count; Malaria; Mice; Neutropenia; Peritoneal Cavity; Plasmodium berghei; Pseudomonas Infections