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-marrow 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.
Keywords: Analysis of Variance; Anemia; Case-Control Studies; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-10; Malaria, Cerebral; Malaria, Falciparum; Severity of Illness Index; Tumor Necrosis Factor-alpha