Role of Th1 and Th2 cytokines in immune response to uncomplicated Plasmodium falciparum malaria

Abstract

The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-gamma), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-gamma, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 +/- 2.8 pg/ml; controls, 3.2 +/- 0.7 pg/ml) and IFN-gamma (39.2 +/- 67.6 pg/ml; controls, 8.4 +/- 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 +/- 2.6 pg/ml), whereas IFN-gamma levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 +/- 200.4 pg/ml and 56.6 +/- 38.4 pg/ml, respectively; controls, 17.4 +/- 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 +/- 1.2 pg/ml; controls, 2.4 +/- 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 +/- 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-gamma levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-gamma may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.

FIG. 1.

Levels of Th1 cytokines, IL-12 and IFN-γ, in sera from 20 patients with uncomplicated P. falciparum malaria and 15 healthy control subjects at day 0 and day 3. The horizontal line within the box stands for the median value; the box includes the 25th and 75th percentiles and the extended T-line stands for standard deviation.

FIG. 2.

Levels of Th2 cytokines, IL-4 and IL-10, in sera from 20 patients with uncomplicated P. falciparum malaria and in 15 healthy control subjects at day 0 and day 3. The horizontal line within the box stands for the median value; the box includes the 25th and 75th percentiles and the extended T-line stands for the standard deviation.

FIG. 3.

Correlation between Th1 cytokines, IL-12 and IFN-γ, and Th2 cytokines, IL-4 and IL-10, and parasitemia on admission in 20 patients with uncomplicated P. falciparum malaria. Correlation coefficients (r²) and their statistical significance (P) are also indicated.