Plasma levels of interleukin 27 in falciparum malaria is increased independently of co-infection with HIV: potential immune-regulatory role during malaria

BMC Infect Dis. 2020 Jan 21;20(1):65. doi: 10.1186/s12879-020-4783-8.

Abstract

Background: The immune response during falciparum malaria mediates both harmful and protective effects on the host; however the participating molecules have not been fully defined. Interleukin (IL)-27 is a pleiotropic cytokine exerting both inflammatory and anti-inflammatory effects, but data on IL-27 in malaria patients are scarce.

Methods: Clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) HIV-1 co-infection, from HIV-infected patients with similar symptoms without malaria (n = 58) and from healthy controls (n = 52). In vitro studies were performed in endothelial cells and PBMC using hemozoin crystals. Samples were analyzed using enzyme immunoassays and quantitative PCR.

Results: (i) IL-27 was markedly up-regulated in malaria patients compared with controls and HIV-infected patients without malaria, showing no relation to HIV co-infection. (ii) IL-27 was correlated with P. falciparum parasitemia and von Willebrand factor as a marker of endothelial activation, but not with disease severity. (iii) In vitro, IL-27 modulated the hemozoin-mediated cytokine response in endothelial cells and PBMC with enhancing effects on IL-6 and attenuating effects on IL-8.

Conclusion: Our findings show that IL-27 is regulated during falciparum malaria, mediating both inflammatory and anti-inflammatory effects, potentially playing an immune-regulatory role during falciparum malaria.

Keywords: Endothelial cells; Falciparum malaria; HIV; Hemozoin; IL-27; Interleukins; PBMC.

MeSH terms

  • AIDS-Related Opportunistic Infections / immunology*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cells, Cultured
  • Coinfection / blood
  • Coinfection / immunology*
  • Cross-Sectional Studies
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Female
  • HIV-1*
  • Hemeproteins / pharmacology
  • Humans
  • Interleukins / blood*
  • Interleukins / genetics
  • Interleukins / immunology*
  • Interleukins / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / immunology*
  • Male
  • Middle Aged
  • Mozambique
  • Parasitemia / immunology
  • Plasmodium falciparum / immunology*
  • Prospective Studies
  • Young Adult

Substances

  • Hemeproteins
  • Interleukins
  • MYDGF protein, human
  • hemozoin