Enhanced response of blood monocytes to in vitro lipopolysaccharide-challenge in patients with recurrent unstable angina

Background-C-reactive protein (CRP) plasma levels have been associated with short- and long-term occurrence of coronary events. We investigated whethe r circulating inflammatory cell responsiveness to low-grade stimuli could c ontribute to the reported association between CRP and coronary events. Methods and Results-We studied 32 patients with unstable angina who were fo llowed for 24 months and were free of symptoms for 6 months (group 1): 19 p atients had persistently high CRP levels (>0.3 mg/dL) (group 1A); 13 patien ts had normal CRP levels (group 1B). During the follow-up, 12 (63%) group 1 A but no group 1B patients developed an infarction or recurrence of unstabl e angina (P<0.001). Eighteen patients with chronic stable angina (group 2) and 18 healthy subjects (group 3) were studied as controls. Interleukin (IL )-6 production (median, range) by peripheral blood mononuclear cells after 4 hours of in vitro stimulation with 1 ng/mL lipopolysaccharide (LPS) was s ignificantly higher in group 1A (4526 pg/mL, 3042 to 10 583 pg/mL) than in group 1B (1752 pg/mL, 75 to 3981 pg/mL), group 2 (707 pg/mL, 41 to 3275 pg/ mL), and group 3 (488 pg/mL, 92 to 3503 pg/mL) (all P<0.001). No significan t differences were observed among the other groups. IL-6 production after L PS-challenge was correlated with baseline CRP levels (r=0.42, P=0.005). Conclusions-Mononuclear cells of patients with recurrent phases of instabil ity exhibit an enhanced production of IL-6 in response to low-dose of LPS, correlated with baseline CRP levels, 6 months after the last acute event. T his persisting enhanced acute-phase responsiveness may help explain the ass ociation between CRP and acute coronary events.