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

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.

Distinct cytokine profiles in malaria coinfections: A systematic review

“… Red, green, and yellow indicate increased, comparable, and decreased cytokine levels between the two groups, respectively. References in the figure [ 33 – 57 , 59 – 61 , 63 – 65 , 83 ]. …”

A population of CD4hiCD38hi T cells correlates with disease severity in patients with acute malaria

“…Possibly adding support to the notion that IL‐27 is driving the CD4 hi CD38 hi phenotype in our patients with acute malaria is a recent paper by Oterdal et al . who found that IL‐27 levels are elevated in the plasma of adults living in malaria‐endemic areas with acute falciparum malaria 44 .…”

Host‐pathogen interaction in the tissue environment during Plasmodium blood‐stage infection

“…Human studies of IL‐27 in malaria are relatively scarce. In a cross‐sectional malaria study in Mozambique, higher plasma levels of IL‐27 in malaria patients correlated with levels of parasitemia; however, there was no correlation with the disease severity 91 . In studies of infants in Togo, however, plasma levels of IL‐27 were lower in malaria cases when compared to infection‐free controls, and the levels remained unchanged after malaria treatment 92 .…”