AbstractAcebutolol induces transient polyclonal B cell activation in C57B1/6 mice but down-modulates the spontaneous polyclonal activation of NZBxNZW lupus mice. The immunomodulatory effects of this beta-blocker were studied in C57B1/6 mice injected with LPS or immunized with sheep red blood cells. The effect of acebutolol on the polyclonal activation of lymphocytes induced by LPS was also investigated in heterozygous and nu/nu C57B1/6 mice. Finally, the direct effet of acebutolol on spleen cells was studied in vitro. Acebutolol treatment for 15 days (50mg/kg/day) inhibited the polyclonal activation of lymphocytes induced by LPS in C57B1/6 and in C57B1/6 nu/nu mice, but increased the humoral response to sheep red blood cells in C57B1/6 mice. Moreover, spleen cells from C57B1/6 mice treated for 15 days with acebutolol showed an increased number of CD5+and CD4+lymphocytes, as well as an increased reactivity to concanavalin A but not to LPS. In vitro, acebutolol at 10−510−7M induced an increased reactivity of spleen cells from naive mice to concanavalin A, whereas it did not affect the B cell responsiveness to LPS. These results indicate that acebutolol modulates both T-cells and non T-cells in the immune system.