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

Kari Otterdal,Thor Ueland,Arne Yndestad,Aase Berg,Annika E Michelsen,Bente Halvorsen,Sam Patel,Ellen Lund Sagen,Pål Aukrust,Nina Langeland,Ida Gregersen

doi:10.1186/s12879-020-4783-8

Abstract

BackgroundThe 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.MethodsClinical 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.ConclusionOur 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.

Highlights

The immune response during falciparum malaria mediates both harmful and protective effects on the host; the participating molecules have not been fully defined
Of the 212 screened patients, 129 had P. falciparum malaria as assessed by qualitative PCR and two had rapid diagnostic test (RDT) and malaria slide positive for P. falciparum giving a total of 131 malaria patients
In malaria patients IL-27 levels were negatively correlated with Estimated glomerulus filtration rate (eGFR), reaching statistical significance in those co-infected with HIV

Summary

Introduction

The immune response during falciparum malaria mediates both harmful and protective effects on the host; the participating molecules have not been fully defined. Falciparum malaria infection triggers a broad range of cytokines [Interleukin (IL)-1ra, IL-6, IL-8, IL-9, IL-10, Eotaxin, Interferon gamma-induced protein 10 (IP10), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1β (MIP-1β) and tumor necrosis factor (TNF)]. Whereas TNF is regarded as a prototypical inflammatory mediator during falciparum malaria promoting organ failure and disease severity [6], the antiinflammatory cytokine IL-10 may be of importance in Otterdal et al BMC Infectious Diseases (2020) 20:65 preventing T cell- and cytokine-mediated pathology during potentially lethal malaria infections [7]. An overwhelming anti-inflammatory response may be harmful for the host, and the identification of protective and harmful mediators and the balance between these molecules during falciparum malaria is far from clear

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