Monocytes responding to oxidized low density lipoprotein (LDL) or other antigens may initiate atherogenesis through production of interleukin-1 (IL-1) and additional cytokines. Interleukin-1 is chemotactic for circulating leukocytes, can stimulate growth of fibroblasts or smooth muscle cells, and causes activation of T- and B-lymphocytes.
Methods
Peripheral blood mononuclear cells (PBMCs) were isolated from 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-1β were measured 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, proliferation in response to arterial antigen was either diminished or unchanged from control values. Peripheral blood mononuclear cells from IHD and control patients had similar levels of proliferation after treatment with different mitogens. Levels of IL-1β, produced after stimulation with arterial antigen or lipopolysaccharide, also did not differ 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-1β. In contrast, PBMCs from 4 patients with unstable angina had increased levels of IL-1β 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 cases with stable angina, and 4.02 ± 5.91 pg/mL for 19 cases with unstable angina). These values reflect a greater than 5-fold increase in variability for IL-1β produced on exposure to oxidized LDL for patients with unstable angina relative to control patients.
Conclusions
Effects 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 IHD. However, PBMCs obtained from a subset of patients with unstable angina produce greater levels of IL-1β after treatment with oxidized, but not native, LDL.
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