Lovastatin Inhibits Proliferation and Differentiation and Causes Apoptosis in Lipopolysaccharide-Stimulated Murine B Cells

Lipopolysaccharide-stimulated murine B lymphocytes were incubated with the pharmacologic drug lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase at concentrations ranging from 10 −5-10 −8M. After 48 hr, treatment with 10 −5M lovastatin inhibited [ 3H] thymidine incorporation 55%. Flow cytometric analysis indicated that the fraction of B cells in S phase was reduced from 26.7% ± 5.44% to 11.6% ± 2.9% when cells were incubated with 10 −5M lovastatin. In addition, a large peak appeared to the left of the G 1 peak that was indicative of apoptosis in cells treated with 10 −5M lovastatin. At 96 hr, the number of plaque-forming B cells was decreased 50% in the presence of lovastatin. Together these results suggest that high concentrations of lovastatin can inhibit B cell proliferation and differentiation of murine B lymphocytes in lipopolysaccharide-activated B cells, perhaps through induction of programmed cell death.