The balance between pro- and antiinflammatory cytokines may be important in
malaria presentation and outcome. Malaria tends to be more severe in child
ren than in adults, presumably because partial immunity develops with age.
However, the fall nature of, and age-related differences in, anti-malarial
immunity are unknown. We compared: (1) serum and cell-specific cytokines of
patients with acute malaria to those of patients with other acute illnesse
s and to those of healthy adults and (2) the cytokine responses of parasite
mic children and parasitemic adults. Flow cytometry was done on the periphe
ral blood mononuclear cells of 148 hospitalized children, 161 febrile hospi
talized adults, and 20 healthy adults in Malawi, Africa, a malaria-endemic
country. Serum cytokines were also assessed for 80 of these patients. Thirt
y-eight participants were parasitemic with Plasmodium falciparum. Serum int
erleukin (IL)-10 (an antiinflammatory, immunoregulatory, and type 2 cytokin
e) levels were higher in malaria patients than in other patients (medians 5
02 pg/mL vs 16 pg/mL, P = 0.002), and the percentages of various lymphocyte
populations making IL-6 (a proinflammatory, type 2 cytokine regulating iro
n distribution) were lower in malaria patients than in other patients (e.g.
, for spontaneous production by children's CD8(+) T cells: medians 1.4% vs
33.1%, P = 0.004). For adult patients, the percentages of lymphocytes spont
aneously making IL-4 (a type 2 cytokine) were significantly lower in those
with malaria than in those without malaria (medians 0.9% vs 2.1%, P = 0.005
). The percentages of monocytes spontaneously making IL-8 (a chemotactic, p
roinflammatory chemokine) were higher in parasitemic children than in parsi
temic adults (medians 5.8% vs 1.7%, P = 0.003). A number of cellular proinf
lammatory, type 1 parameters were significantly higher in all children (wit
h or without malaria) than in all adults; these included the percentages of
various lymphocyte populations making IL-6, both IL-6 and interferon-gamma
, or IL-8. These data support the importance of IL-10 in malaria parasitemi
a. Given the lack of an IL-4 (type 2) response, IL-10's primary role may be
immunoregulatory rather than type 2 in nature. In this study, the immune r
esponse to malaria was more proinflammatory in children than in adults. Thi
s difference, if corroborated by other studies, could be related to malaria
's greater severity in children. (C) 2001 Academic Press.