Phagocyte function in familial hypercholesterolaemia: peripheral blood monocytes exposed to lipopolysaccharide show increased tumour necrosis factor production.

We studied functions of polymorphonuclear leucocytes (PMN) and monocytes from peripheral blood of subjects with familial hypercholesterolaemia (FH). FH monocytes exposed to Escherichia coli lipopolysaccharide (LPS) in 10% human AB serum generated tumour necrosis factor (TNF) significantly more than did control monocytes. After lowering of serum low-density lipoprotein (LDL) levels by drug treatment, FH monocytes exposed to LPS in the absence of exogenous lipoproteins generated significantly more TNF than did control monocytes. These findings suggest that increased TNF production is not affected by hypolipidaemic treatment and may not derive from differences between uptake of exogenous LDL by FH monocytes and control cells. Chemotaxis, chemokinesis, and random migration of both FH PMN and FH monocytes were normal, as determined by agarose assay and membrane filter assay. FH PMN showed increased luminol-enhanced chemiluminescence in response to 2.5 x 10(-8) M, but not to 2.5 x 10(-6) M, N-formyl-methionyl-leucyl-phenylalanine, and not to serum-treated zymosan or to phorbol myristate acetate. Luminol- and lucigenin-enhanced chemiluminescence responses of FH monocytes were normal. In summary, the major aberration found in the present study was that FH monocytes stimulated with LPS show enhanced production of TNF. The possibility that exaggerated TNF production contributes to an early development of atherosclerotic lesions in FH subjects warrants further studies.