LPS-induced cytokine production and expression of beta2-integrins and CD14 by peripheral blood mononuclear cells of patients with homozygous familial hypercholesterolemia.
It has been suggested that proinflammatory cytokines such as tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1), as well as adhesion molecules such as beta2-integrins and CD14, play a role in the pathogenesis of atherosclerosis. Familial hypercholesterolemia (FH) is an autosomal disease in which defective or absent LDL receptors are the cause for extreme LDL concentrations and early development of atherosclerosis. We studied lipopolysaccharide-induced cytokine production and the expression of adhesion molecules by mononuclear cells of three homozygous FH patients and compared them with first-degree relatives and healthy controls. There was a tendency towards increased cytokine production by cells of FH patients, whereas the expression of adhesion molecules was not modified compared to controls. In addition, LDL-apheresis inhibited IL-1 and TNF production and the expression of CD11a, CD11b, CD11c and CD14 by the mononuclear cells of FH patients and this may be an additional beneficial effect of LDL-apheresis apart of decreasing LDL concentrations.
Rovers
C
C
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Netea
M G
MG
de Bont
N
N
Demacker
P N
PN
Jacobs
C
C
Kullberg
B J
BJ
Van der Meer
J W
JW
Stalenhoef
A F
AF
D000293:Adolescent; D000328:Adult; D018821:CD18 Antigens / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics; D007375:Interleukin-1 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol