Peripheral blood mononuclear cells and cytokine profile in severe and uncomplicated malaria patients in Sri Lanka
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Date
2003
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University of Colombo: UC(MED).
Abstract
Human peripheral blood mononuclear cell responses to P. falciparum and P. vivax were studied by measuring the changes in the cell counts during acute malaria infections. Plasma cytokines such as TNF-alpha, IL-4, IFN-gama, serum IgE and serum IgG levels were measured and these levels were related to the degree of disease severity, the endemicity of the area of residence of the patient and species diversity. Samples were taken from the National Hospital of Sri Lanka and General Hospital, Anuradhapura. Cytokine specific mRNA levels of IL-6, IL-10 and IFN- gama were measured in uncomplicated P. falciparum patients and plasma cytokine levels and cytokine specific mRNA levels were correlated. The total leucocyte count was lower in malaria patients as compared to healthy vontrols and the results indicates that lymphopenia is mainly due to reduction in alpha-beta T-cells. With increasing parasitaemia, both peripheral blood mononuclear cell count and alpha-beta counts decreased. Significantly higher gamma-delta T-cell count in severe malaria patients compared to uncomplicated P. falciparum patients and the association between gamma-delta T-cells are indeed associated with the pathology of disease. Cytokine concentrations in plasma do not directly reflect the frequencies of cytokine producing peripheral blood mononuclear cell count. According to this study one of the reasons for clinical disease in severe malaria infections and P. vivsx infections is higher levels of Th2 responses. Mutual inhibition of Th1 and Th2 cytokines in malaria was further confirmed. Adjusting for parasite density, days of sympotoms, and number of past malarial infections resulted in significant differences between the two species, being seen only for IL-10 and IgG levels. In uncomplicated malaria clinical score, a measure of disease severity, was dependent on plasma a higher score having IL-10 levels. The association of IL-10 levels with parasitaemia, and clinical disease, suggests that IL-10 plays a role in the pathogenesis of malaria. High levels of serum IgG may be playing a protective role in P. vivx infections despite having high levels of cytokines in the peripheral blood. Low level of clinical score in uncomplicated P. falciparum and P. vivaxinfections from endemic regions compared to non-endemic regions suggests the presence of anti-disease immunity in malaria patients from endemic regions in Sri Lanka. All three groups of malaria patients form malaria patients from malaria endemic areas had lower peripheral blood mononuclear cell count as compared to their non-endemic counterparts providing evidence for immunosuppression of the host to malaria antigens in Sri Lanka. IFN-gamma levels were significantly higher in uncomplicated P. falciparum patients from endemic regions as compared to patients from non-endemic regions providing evidence of a protective role for IFN-gamma. According to our results some of the factors that may contribute to the higher degree of clinical disease of both P.vivax and P. falciparum patients in non-endemic areas are higher levels of cytokines such as IL-10, TNF- alpha and IgE. The relatively high plasma cytokine levels in non-endemic patients could also have been due to less responsiveness of peripheral blood mononuclear cells to parasite antigens in clinically immune endemic patients.
Description
Dissertation: PhD, University of Colombo: UC(MED), 2003.
Keywords
Malaria
Citation
PERERA, RASK, Peripheral blood mononuclear cells and cytokine profile in severe and uncomplicated malaria patients in Sri Lanka, University of Colombo UC(MED), 2003: xxvi, 161p.