Activation of nuclear factor kappa B in peripheral blood mononuclear cells from malaria patients.
BACKGROUND
Malaria parasites and their products can activate a specific immune response by stimulating cytokine production in the host's immune cells. Transcription nuclear factor kappa B (NF-κB) is an important regulator for the control of many pro-inflammatory genes, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). The activation and expression of NF-κB p65 in peripheral blood mononuclear cells (PBMCs) of malaria patients were investigated and correlated with the levels of IL-10 and TNF to study the nature of NF-κB p65 and its linkage to inflammatory cytokines.


METHODS
The sample group comprised 33 patients admitted with malaria caused by Plasmodium vivax (n = 11), uncomplicated Plasmodium falciparum (n = 11), and complicated Plasmodium falciparum (n = 11). Peripheral blood was collected at admission and on day 7 for PBMC isolation. Healthy subjects were used as a control group. The expressions of NF-κB p65 in the PBMCs from malaria patients and the plasma levels of IL-10 and TNF were measured by using enzyme-linked immunosorbent assay (ELISA). The immunofluorescence technique was used to determine NF-κB nuclear translocation.


RESULTS
At admission, patients with P. vivax and uncomplicated P. falciparum had significantly elevated phospho-NF-κB p65 levels in the PBMCs compared with those of healthy controls. However, patients with complicated P. falciparum malaria had decreased levels of phospho-NF-κB p65. On day 7 post-treatment, significantly increased phospho-NF-κB p65 was found in the PBMCs of patients with complicated P. falciparum, compared with healthy controls. The plasma level of IL-10 was elevated in day 0 in patients with complicated P. falciparum malaria and was found to be negatively correlated with phospho-NF-κB p65 level (rs = -0.630, p = 0.038). However, there was no correlation between phospho-NF-κB p65 expression and TNF level in patients with complicated P. falciparum malaria.


CONCLUSIONS
This is the first report demonstrating alterations in NF-κB p65 activity in the PBMCs of malaria patients. The altered lower features of NF-κB p65 in the PBMCs of patients with complicated P. falciparum at admission could be due to a suppressive effect of high IL-10 associated with complicated P. falciparum malaria.
Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand.
Chuchard
C
Punsawad
Srivicha
S
Krudsood
Yaowapa
Y
Maneerat
Urai
U
Chaisri
Noppadon
N
Tangpukdee
Emsri
E
Pongponratn
Kwannan
K
Nantavisai
Rachanee
R
Udomsangpetch
Parnpen
P
Viriyavejakul
D000293:Adolescent; D000328:Adult; D001769:Blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D051996:Transcription Factor RelA / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10