The implications of high levels of the immune regulatory cytokine IL-10 in Plasmodium falciparum malaria are unclear. IL-10 may down-regulate pro-inflammatory responses and also exacerbate disease by inhibiting anti-parasitic immune functions. To study possible inhibiting effects on parasite clearance, IL-10 plasma levels were determined in 104 Tanzanian children, 1 to 4 years old, with acute uncomplicated P. falciparum malaria, and analysed for association with parasite densities during 3 days of anti-malarial treatment. Higher baseline IL-10 plasma levels were associated with statistically significantly higher parasite densities after 24, 48 and 72 h of treatment. These associations could not be explained by differences in initial parasitaemia, temperature, age, sex or type of treatment. Induction of high IL-10 production might be a direct or indirect mechanism whereby the parasite evades the immune response.

Abstract. Sulfadoxine/pyrimethamine (SP) is increasingly used against malaria in sub-Saharan Africa because of chloroquine resistance. However, chloroquine may have a beneficial antipyretic effect. We therefore compared the combination of SP plus chloroquine, chloroquine alone, SP alone, and SP plus paracetamol in the treatment of uncomplicated Plasmodium falciparum malaria in 175 Tanzanian children (1−4 years old) in a randomized trial. Outcome variables were axillary temperatures every six hours, daily parasitemias, and serum levels of IgG antibodies to P. falciparum. Lower mean temperatures (6−48 hours) were achieved with SP plus chloroquine or paracetamol than with SP alone (P < 0.001) or chloroquine alone (P < 0.05). All three SP-treated groups showed high and similar parasite reduction (0−48 hours), whereas treatment with chloroquine alone was much less effective. Levels of IgG antibodies to P. falciparum increased significantly (P < 0.001) and similarly in the four treatment groups between days 0, 2. and 3. Thus, the addition of chloroquine or paracetamol to SP improved the clinical outcome, but did not affect the parasitologic response or antibody production.

Chloroquine is prescribed as both an anti-malarial and an anti-inflammatory drug. However, its immunomodulating effects remain largely unclear. Previous studies have shown that chloroquine inhibits antigeninduced proliferation, implying immuno-suppressive effects. In this study, we examined whether the inhibition of the proliferation reflects changes in the surface molecules that are important for T-cell activation and whether chloroquine affects the balance between pro-and anti-inflammatory cytokines. Chloroquine elevated the expression of the costimulatory and adhesion molecules B7-2 (CD86) and ICAM-1 (CD54) in peripheral mononuclear cells (PBMC). An increased percentage of CD14 cells was also observed, and within this cell population, an increase in ICAM-1 expression was revealed by double-staining experiments. Assessment of the frequencies of interleukin (IL)-10 and interferon (IFN)-g-producing cells in in vitro-cultivated PBMCs showed that the ratio between pro-and antiinflammatory cytokines changed after exposure to chloroquine, favouring anti-inflammatory immune responses. This effect was mainly because of increased frequencies of IL-10-producing cells and was seen with or without the presence of stimulating antigens or mitogens. Our findings indicate that chloroquine affects the direction of the lymphocyte stimulation towards an anti-inflammatory response by affecting the antigen-presenting cells (APC) and the balance between pro-and anti-inflammatory cytokines, rather than generally inhibiting cytokine production.