The role of immune activation in endotoxin-induced atherogenesis

Some infectious agents may contribute to atherosclerosis by maintaining a h eightened state of inflammatory response. Although the risk for atheroscler osis was associated with elevated plasma levels of endotoxin. it is difficu lt to firmly establish what place endotoxin assumes in the etiology of this disease. As the ability for endotoxin to promote disease may depend on its ability to initiate an inflammatory response. it may be controlled by addi tional regulatory factors. We measured plasma levels of endotoxin and serum levels of neopterin and soluble interleukin-2 receptor in a random populat ion of 402 men and women. 50-79 years old at the 1990 baseline evaluation ( Bruneck Study). End point of the prospective survey was incident (early) at herosclerosis in the carotid arteries as assessed with duplex ultrasound. S ubjects with high endotoxin levels (90th percentile) in combination with lo w neopterin or soluble interleukin-2 receptor levels (below median) did not differ from those with low endotoxin in their risk of incident atheroscler osis. The risk associated with high endotoxin. however. was markedly elevat ed in subjects with high (above median) neopterin or soluble interleukin-2 receptor levels. The study provides epidemiological evidence that the ather ogenic potential of endotoxemia is affected by concomitant immune activatio n.