title: Distinct cytokine profiles define clinical immune response to falciparum malaria in regions of high or low disease transmission.
abstract: The immune effector response to Plasmodium falciparum infection involves a finely-tuned interplay 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.
authors.affiliation: Division of Molecular and Structural Biology, Central Drug Research Institute, Chattar Manzil, Mahatma Gandhi Marg, Lucknow, India.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Sinha
authors.forename: Tabish
authors.initials: T
authors.lastname: Qidwai
authors.forename: Kanika
authors.initials: K
authors.lastname: Kanchan
authors.forename: Ganga N
authors.initials: GN
authors.lastname: Jha
authors.forename: Prerna
authors.initials: P
authors.lastname: Anand
authors.forename: Sudhanshu S
authors.initials: SS
authors.lastname: Pati
authors.forename: Sanjib
authors.initials: S
authors.lastname: Mohanty
authors.forename: Saroj K
authors.initials: SK
authors.lastname: Mishra
authors.forename: Prajesh K
authors.initials: PK
authors.lastname: Tyagi
authors.forename: Surya K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Shally
authors.initials: S
authors.lastname: Awasthi
authors.forename: Vimala
authors.initials: V
authors.lastname: Venkatesh
authors.forename: Saman
authors.initials: S
authors.lastname: Habib
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D003710:Demography; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D058408:Th1-Th2 Balance; D055815:Young Adult
chemical_list: D016207:Cytokines