Low plasma concentrations of interleukin-10 in severe malarial anaemia compared with cerebral and uncomplicated malaria

Background. Severe anaemia is a major complication of malaria but little is known about its pathogenesis. Experimental models have implicated tumour necrosis factor (TNF) in induction of bone-marow suppression and eythrophagocytosis. Conversely, interleukin 10 (IL-10), which mediates feed-back regulation of TNF, stimulates bone-marrow function in vitro and counteracts anaemia in mice. We investigated the associations of these cytokines with malarial anaemia. Methods. We enrolled 175 African children with malaria into two studies in 1995 and 1996. In the first study, children were classified as having severe anaemia (n = 10), uncomplicated malaria (n = 26), or cerebral anaemia (n = 41). In the second study, patients were classified as having cerebral malaria (n = 33) or being fully conscious (n = 65), and the two groups were subdivided by measured haemoglobin as normal (> 110 g/L), moderate anaemia (60-90 g/L), and severe anaemia (< 50 g/L). IL-10 and TNF concentrations were measured by ELISA in plasma samples from all patients. Findings. IL-10 concentrations were significantly lower in patients with severe anaemia than in all other groups. In 1995, geometric mean plasma IL-10 in patients with severe anaemia was 270 pg/mL (95% CI 152-482) compared with 725 pg/mL (465-1129) in uncomplicated malaria and 966 pg/mL (612-1526) in cerebral malaria (p < 0.03). In 1996, fully conscious patients with severe anaemia also had significantly lower IL-10 concentrations than all other groups, including cerebral-malaria patients with severe anaemia and all patients with moderate anaemia (p < 0.001). In both studies, TNF concentrations were significantly higher in cerebral malaria than in fully conscious patients (p < 0.01). By contrast, the ratio of TNF to IL-10 was significantly higher in fully conscious patients with severe anaemia than in all other groups (p < 0.001). Interpretation. Our findings identify severe malarial anaemia as a distinct disorder in which insufficient IL-10 response to high TNF concentrations may have a central role.