SYSTEMIC ENDOTHELIAL ACTIVATION OCCURS IN BOTH MILD AND SEVERE MALARIA - CORRELATING DERMAL MICROVASCULAR ENDOTHELIAL-CELL PHENOTYPE AND SOLUBLE CELL-ADHESION MOLECULES WITH DISEASE SEVERITY

Fatal Plasmodium falciparum malaria is accompanied by systemic endothe lial activation. To study endothelial activation directly during malar ia and sepsis in vivo, the expression of cell adhesion molecules on de rmal microvascular endothelium was examined in skin biopsies and corre lated with plasma levels of soluble (circulating) ICAM-1, E-selectin, and VCAM-1 and the cytokine tumor necrosis factor (TNF)-alpha. Skin bi opsies were obtained from 61 cases of severe malaria, 42 cases of unco mplicated malaria, 10 cases of severe systemic sepsis, and 17 uninfect ed controls. Systemic endothelial activation, represented by the up-re gulation of inducible cell adhesion molecules (CAMs) on endothelium an d increased levels of soluble CAMs (sCAMs), were seen in both severe a nd uncomplicated malaria and sepsis when compared with uninfected cont rols. Plasma levels of sICAM-1, sVCAM-1, and sE-selectin correlated po sitively with the severity of malaria whereas TNF-alpha was raised non specifically in malaria and sepsis. Immunohistochemical evidence of en dothelial activation in skin biopsies did not correlate with sCAM leve ls or disease severity. This indicates a background of systemic endoth elial activation, which occurs in both mild and severe malaria and sep sis, The levels of sCAMs in malaria are thus not an accurate reflectio n of endothelial cell expression of CAMs in a particular vascular bed, and other factors must influence their levels during disease.