Cytokine response during non-cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults

Abstract

Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoan Plasmodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasmodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death.Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines.Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria.Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.

MCP-1, KC-like and IL-8 as critical mediators of pathogenesis caused by Babesia canis

“…In recent studies about malaria, levels of pro-inflammatory biomarkers, like IL-8, were higher in cerebral malaria (CM) than in non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines, like IL-10, were comparable or lower in CM patients [ 55 ]. We observed a similar pattern: higher MCP-1 levels in complicated cases and increasing levels of IL-8 in the period studied (day 1 to 7), in remarkable contrast with the decrease observed in B .…”

Circulating Cytokine Profiles of Polyparasitized Individuals in Gabon.

“…Plasmodium-infected participants with. TNF-α is the cytokine most implicated in the development of the clinical signs of malaria [30], whilst IL-10 and IL-6 are present at high levels in patients with symptomatic malaria [31][32][33]. The asymptomatic status of participants at the time of the study presented here could indicate the acquisition of premunition which limits the appearance of clinical symptoms, and/or that participants were sampled at an early stage of the infection, before progression toward symptomatic disease [34].…”

Circulating Cytokine Profiles of Polyparasitized Individuals in Gabon.

“…TNF-α did not vary in the control group compared to Plasmodium-infected participants with. TNF-α is the cytokine most implicated in the development of the clinical signs of malaria [31], whilst IL-10 and IL-6 are present at high levels in patients with symptomatic malaria [32][33][34]. The asymptomatic status of participants at the time of the study presented here could indicate the acquisition of premunition which limits the appearance of clinical symptoms, and/or that participants were sampled at an early stage of the infection, before progression toward symptomatic disease [35].…”