ArticlesLow plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria
Introduction
Severe malarial anaemia is one of the most important complications of malaria in African children and carries a high mortality rate in areas of intense Plasmodium falciparum transmission.1 The pathogenesis of severe anaemia has, however, received little attention. Increased destruction of infected and uninfected red blood cells and suppression of erythropoiesis seem to be important causative factors of severe anaemia.2 These mechanisms are generally present in all malaria cases, and whether severe anaemia represents the extreme of a continuum of pathology or constitutes a separate disease entity is not clear.
In a previous study, we showed that bone-marrow inhibition in human malaria was not due to defective erythropoietin production.3 Increased destruction of red blood cells4 and bone-marrow suppression5 have been associated with tumour necrosis factor (TNF) in experimental murine malaria. Repeated injections of TNF causes chronic anaemia in rats,6 but the importance of TNF in severe malarial anaemia in human beings has not been studied. TNF is a proinflammatory cytokine, concentrations of which are raised in patients with malaria, especially those with cerebral malaria.7, 8 The production of TNF is downregulated by anti-inflammatory cytokines such as interleukin 10 (IL-10),9 which also has raised concentrations in malaria.10 IL-10 stimulates bone-marow formation in murine osteogenic stroma,11 and IL-10-deficient mice develop severe anaemia.12 To investigate a possible role for TNF and IL-10 in severe malarial anaemia, we measured plasma concentrations of TNF and IL-10 in Ghanaian children with severe anaemia, cerebral malarial, or uncomplicated malaria, and in healthy children with similar exposure to P falciparum infection.
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Patients and methods
Children admitted during the malaria season (June to August) of 1995 and 1996 to the emergency room at the Department of Child Health, Korle-Bu Teaching Hospital, Ghana, were included. The general inclusion criteria were asexual P falciparum parasitaemia of more than 10 000/μL (in 1996, >1 parasite per white blood cell) and axillary temperature of more than 37·5°C. Children with any disease other than malaria or with a positive sickling test (metabisulphite method) were excluded from the study.
Results
In 1995, 41 patients with cerebral malaria, ten with severe anaemia, and 26 with uncomplicated malaria were enrolled (table 1). Parasitaemias were generally high on admission in all groups. Geometric mean parasite density per μL was 82 000 (95% CI 30 000–222 000), 108 000 (59 000–207 000), and 75 000 (46 000–120 000) in severe anaemia, cerebral, and uncomplicated malaria, respectively (p=0·45). Whereas haemoglobin concentrations formed part of the definition of uncomplicated malaria and severe
Discussion
Acute malaria is associated with the destruction of infected red blood cells and non-responsiveness of the bone marrow to the resulting drop in haemoglobin.3, 16 Severe malarial anaemia may, therefore, constitute the extreme end of a continuum of haemoglobin values. However, we found strikingly lower IL-10 concentrations in patients with severe anaemia than in patients with moderate anaemia or cerebral malarial, which suggests that severe anaemia has a specific pathology. One study suggested
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