Distinct patterns of cytokine regulation in discrete clinical forms of Plasmodium falciparum malaria

TY - JOUR

T1 - Distinct patterns of cytokine regulation in discrete clinical forms of Plasmodium falciparum malaria

AU - Akanmori, B D

AU - Kurtzhals, J A

AU - Goka, B Q

AU - Adabayeri, V

AU - Ofori, M F

AU - Nkrumah, F K

AU - Behr, C

AU - Hviid, L

N1 - Keywords: Anemia; Antigens, CD; Child; Child, Preschool; Cytokines; E-Selectin; Ghana; Humans; Intercellular Adhesion Molecule-1; Interferon Type II; Interleukin 1 Receptor Antagonist Protein; Interleukins; Malaria, Cerebral; Malaria, Falciparum; Receptors, Interleukin-2; Receptors, Interleukin-4; Receptors, Interleukin-6; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Regression Analysis; Sialoglycoproteins; Tumor Necrosis Factor-alpha

PY - 2000

Y1 - 2000

N2 - The pathogenesis of two of the most severe complications of Plasmodium falciparum malaria, cerebral malaria (CM) and severe malarial anaemia (SA) both appear to involve dysregulation of the immune system. We have measured plasma levels of TNF and its two receptors in Ghanaian children with strictly defined cerebral malaria (CM), severe malarial anaemia (SA), or uncomplicated malaria (UM) in two independent studies in an area of seasonal, hyperendemic transmission of P. falciparum. Levels of TNF, soluble TNF receptor 1 (sTNF-R1) and 2 (sTNF-R2) were found to be significantly higher in CM than in the other clinical categories of P. falciparum malaria patients. Levels of both receptors depended on clinical category, whereas only sTNF-R1 levels were significantly dependent on parasitemia. Detailed analysis of the interrelationship between these variables resolved this pattern further, and identified marked differences between the patient categories. While levels of TNF, sTNF-R1 and sTNF-R2 correlated with parasitemia in UM, this was not the case in CM and SA. Rather, there was a tendency towards high levels of TNF and its receptors in CM and low levels in SA without significant correlation to parasitemia in either category. This, and the fact that malaria-induced increases in plasma levels of IL-10 are much lower in SA compared to CM, suggest that distinct forms of dysregulation of the immune response to infection contribute to the pathogenesis of CM and SA.

AB - The pathogenesis of two of the most severe complications of Plasmodium falciparum malaria, cerebral malaria (CM) and severe malarial anaemia (SA) both appear to involve dysregulation of the immune system. We have measured plasma levels of TNF and its two receptors in Ghanaian children with strictly defined cerebral malaria (CM), severe malarial anaemia (SA), or uncomplicated malaria (UM) in two independent studies in an area of seasonal, hyperendemic transmission of P. falciparum. Levels of TNF, soluble TNF receptor 1 (sTNF-R1) and 2 (sTNF-R2) were found to be significantly higher in CM than in the other clinical categories of P. falciparum malaria patients. Levels of both receptors depended on clinical category, whereas only sTNF-R1 levels were significantly dependent on parasitemia. Detailed analysis of the interrelationship between these variables resolved this pattern further, and identified marked differences between the patient categories. While levels of TNF, sTNF-R1 and sTNF-R2 correlated with parasitemia in UM, this was not the case in CM and SA. Rather, there was a tendency towards high levels of TNF and its receptors in CM and low levels in SA without significant correlation to parasitemia in either category. This, and the fact that malaria-induced increases in plasma levels of IL-10 are much lower in SA compared to CM, suggest that distinct forms of dysregulation of the immune response to infection contribute to the pathogenesis of CM and SA.

M3 - Journal article

C2 - 10705308

SN - 1148-5493

VL - 11

SP - 113

EP - 118

JO - European Cytokine Network

JF - European Cytokine Network

IS - 1

ER -