title: Cytokine network in adults with falciparum Malaria and HIV-1: increased IL-8 and IP-10 levels are associated with disease severity.
abstract: BACKGROUND
  Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection.
  
  
  METHODS
  This was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines.
  
  
  RESULTS
  We included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization.
  
  
  CONCLUSIONS
  Our findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria.
authors.affiliation: Department of Medicine, Stavanger University Hospital, Stavanger, Norway; Department of Medicine, The Central Hospital of Maputo, Maputo, Mozambique; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Aase
authors.initials: A
authors.lastname: Berg
authors.affiliation: Department of Medicine, The Central Hospital of Maputo, Maputo, Mozambique.
authors.forename: Sam
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Medicine, The Central Hospital of Maputo, Maputo, Mozambique.
authors.forename: Miguel
authors.initials: M
authors.lastname: Gonca
authors.affiliation: Department of Medicine, The Central Hospital of Maputo, Maputo, Mozambique.
authors.forename: Catarina
authors.initials: C
authors.lastname: David
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Research Department, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Ingvild
authors.initials: I
authors.lastname: Dalen
authors.affiliation: Research Department, Stavanger University Hospital, Stavanger, Norway; Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kvaløy
authors.affiliation: Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway; Institute of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Research Laboratory Nordland Hospital, Bodø, Norway; Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors.forename: Tom E
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Langeland
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000378:metabolism*; D060085:Coinfection / Q000378:metabolism* / Q000401:mortality; D005260:Female; D015658:HIV Infections / Q000378:metabolism* / Q000401:mortality; D015497:HIV-1 / Q000502:physiology*; D006761:Hospitals / Q000706:statistics & numerical data; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009073:Mozambique / Q000453:epidemiology; D055815:Young Adult
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016209:Interleukin-8