Open Access

ARTICLE

Distinct cytokine profiles define clinical immune response to falciparum malaria in regions of high or low disease transmission

Swapnil Sinha¹, Tabish Qidwai¹, Kanika Kanchan¹, Ganga N. Jha¹, Prerna Anand², Sudhanshu S. Pati³, Sanjib Mohanty³, Saroj K. Mishra³, Prajesh K. Tyagi⁴, Surya K. Sharma⁴, Shally Awasthi², Vimala Venkatesh², Saman Habib¹

1 Division of Molecular and Structural Biology, Central Drug Research Institute, Lucknow, India
2 King George Medical University (KGMU), Lucknow, India
3 Ispat General Hospital, Rourkela, India
4 Rourkela Field Station (National Institute of Malaria Research), Rourkela, India

* Corresponding Author: S. Habib,

European Cytokine Network 2010, 21(4), 232-240. https://doi.org/10.1684/ecn.2010.0208

Accepted 31 July 2010;

Abstract

The immune effector response to Plasmodium falciparum infection involves a finely-tuned inter-play between different cell types and cytokines. However, the processes by which they mediate the development of clinical immunity, in areas of different endemicity, are poorly understood. We analyzed circulating levels of pro-inflammatory (TNF, IFN-γ, IL-12, IL-16) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines in control and patient groups drawn from a P. falciparum-endemic and a non-endemic region of India. The endemic region control population exhibited a lower pro- to anti-inflammatory cytokine ratio, indicating a shift towards a high basal Th2 response. Levels of IL-10 contributed most towards the region-specific difference in basal cytokine response. IL-10 was also the strongest predictor of disease in the endemic region, while IL-12, along with IL-10 and IL-6, contributed most to disease outcome in the non-endemic region. A low, mean IFN-γ/IL-10 ratio was associated with disease severity in the endemic region (p < 0.0001). In contrast, a low mean IL-12/IL-10 ratio correlated with disease outcome in the non-endemic region (p < 0.0001). In the endemic region, IL-13 correlated negatively with IFN-γ in severe patients (Spearman’s ρ: -0.49; p : 0.013), while in the non-endemic region, IL-13 correlated negatively with IL-6 in severe malaria patients (Spearman’s ρ: -0.485; p : 0.001). In conclusion, levels of pro- and anti-inflammatory cytokines and the relative balance between the Th1 and Th2 response, illustrates how populations residing in areas of varying disease endemicity may respond to P. falciparum-induced immune challenge.

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