Complement activation in severe Plasmodium falciparum malaria.
We determined indices of plasma complement activation (C3, C4, Bb, C4d, iC3b, and SC5b-9), levels of tumor necrosis factor (TNF) and interleukin-6, and the APACHE II score in 23 patients with complicated Plasmodium falciparum malaria. On admission, plasma concentrations of Bb, SC5b-9, and C4d were markedly increased compared to healthy control subjects (n = 24) (4.5 +/- 1.9 vs 1.5 +/- 0.6 mg/L; 1125.7 +/- 496.9 vs 183.2 +/- 76.5 microg/L; and 15.7 +/- 5.7 vs 7.2 +/- 1.4 mg/L, P < 0.01 for all). In contrast C3 and iC3b concentrations were decreased (631.4 +/- 247 vs 947.3 +/- 243.2 and 105 +/- 17.9 vs 151.3 +/- 14.5 mg/L; P < 0.01 for both). Plasma C4 concentrations in malaria were not different from normal controls. Plasma Bb, C3, and iC3b levels normalized on day 7 of treatment, whereas SC5b-9 and C4d levels remained elevated. A significant correlation between elevated TNF levels and Bb (r = 0.507) and SC5b-9 (r = 0.448, P < 0.01 for both) and a negative correlation between iC3b and SC5b-9 and TNF levels existed (r = -0.537 and r = -0.466, P < 0.01 for both). In addition, a significant correlation between C3 and iC3b (r = 0.689) and C4 and C4d (r = 0.737) existed. However, no relation between clinical disease severity and complement fragments existed. The results demonstrate that both the classical and the alternative pathways of the complement system are profoundly activated in complicated malaria.
Wenisch
C
C
Internal Medicine I, University of Vienna, Vienna, Austria.
Spitzauer
S
S
Florris-Linau
K
K
Rumpold
H
H
Vannaphan
S
S
Parschalk
B
B
Graninger
W
W
Looareesuwan
S
S
D000328:Adult; D003167:Complement Activation; D003176:Complement C3 / Q000032:analysis; D003179:Complement C3b / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D015935:Complement C4b; D011415:Complement Factor B / Q000032:analysis; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology*; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D003176:Complement C3; D003181:Complement C4; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D003179:Complement C3b; D015935:Complement C4b; C032261:complement C4d; D011415:Complement Factor B