INTERLEUKIN-1 RESPONSE TO ARTERIAL ANTIGEN, LIPOPOLYSACCHARIDE, AND OXIDIZED LOW-DENSITY-LIPOPROTEIN IN ISCHEMIC-HEART-DISEASE

Background: Monocytes responding to oxidized low density lipoprotein ( LDL) or other antigens may initiate atherogenesis through production o f interleukin-1 (IL-I) and additional cytokines, Interleukin-1 is chem otactic for circulating leukocytes, can stimulate growth of fibroblast s or smooth muscle cells, and causes activation of T-and B-lymphocytes , Methods: Peripheral blood mononuclear cells (PBMCs) were isolated fr om 42 patients with angiographically verified ischemic heart disease ( IHD) and 35 age-matched control subjects without a history of cardiac disease, Rates of proliferation and production of IL-1 beta were measu red after peripheral blood mononuclear cells were cultured for 7 days in the presence of mitogens, arterial antigen, lipopolysaccharide, or native and oxidized forms of LDL. Results: In patients with IHD, proli feration in response to arterial antigen was either diminished or unch anged from control values, Peripheral blood mononuclear cells from IHD and control patients had similar levels of proliferation after treatm ent with different mitogens, Levels of IL-1 beta, produced after stimu lation with arterial antigen or lipopolysaccharide, also did not diffe r for PBMCs obtained from control and IHD patients, For patients with either a stable angina pattern or no history of cardiac disease, PBMC cultured in the presence of native and oxidized forms of LDL released similar amounts of IL-1 beta, In contrast, PBMCs from 4 patients with unstable angina had increased levels of IL-1 beta after culture in the presence of oxidized LDL (group means +/- standard deviation of 1.63 +/- 1.08 pg/mL for 17 control patients, 0.96 +/- 0.23 pg/mL for 4 case s with stable angina, and 4.02 +/- 5.91, pg/mL for 19 cases with unsta ble angina), These values reflect a greater than 5-fold increase in va riability for IL-1 beta produced on exposure to oxidized LDL fur patie nts with unstable angina relative to control patients, Conclusions: Ef fects of in vitro stimulation with mitogens or lipopolysaccharide are similar for PBMC obtained from normal or IHD patients, The response to arterial antigen is also not increased in cells from patients with IH D, However, PBMCs obtained fi om a subset of patients with unstable an gina produce greater levels of IL-1 beta after treatment with oxidized , but not native, LDL.