Inflammatory cytokine responses in children with asymptomatic malaria infection living in rural, semi-urban and urban areas in south-eastern Gabon

Abstract

Cytokines are soluble mediators of the immune response, and their evolution influences the disease outcome. Gaining knowledge on cytokines has become important, as they can constitute biomarkers allowing the diagnosis of malaria and preventing severe forms of the disease. Here, we investigated 10 cytokines and their circulating levels in asymptomatic Gabonese children with Plasmodium falciparum infection living in urban, semi-urban and rural areas. Blood samples were collected from 273 schoolchildren (153 uninfected and 120 infected) aged 6 to 192 months. Hematological parameters were determined and P. falciparum diagnosis was performed using a rapid diagnosis test, microscopy and nested polymerase chain reaction (PCR). Plasma pro- [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12p70, IL-17A and IL-22] and anti-inflammatory [IL-10, IL-4, IL-13 and transforming growth factor (TGF)-β] cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA) and compared between asymptomatic-infected and uninfected children. Results revealed that without distinction of area, IL-10 and IL-6 levels were higher in infected compared to uninfected children; however, the pro- and anti-inflammatory ratios (IL-6/IL-10 and TNF-α/IL-10) were similar. Furthermore, with area distinction significantly elevated levels of IL-10 in these asymptomatic children were always accompanied by either significantly low or high levels of a proinflammatory cytokine. Also, comparison between asymptomatic-infected children from the three areas showed significantly lower IL-17A, IL-22 and TGF-β levels in urban area compared to semi-urban and rural areas. These results suggest that asymptomatic malaria infections induce significantly high inflammatory cytokine levels without modifying the balanced between pro- and anti-inflammatory cytokines and underline the higher exposure to infections of children in rural areas.