beta-Hydroxy-beta-methylbutyrate modifies human peripheral blood cell proliferation and cytokine production in vitro

Objective: The main objective was to investigate the potential immunomodulatory effects of beta-hydroxy-beta-methylbutyrate (HMB) in human cells. Methods: Peripheral blood mononuclear cells were isolated from the blood of eight volunteers and assayed for proliferation, cell cycle progression, surface expression of CD25, intracellular expression of pERK1/2, and cytokine production after in vitro exposure to a range of HMB concentrations (0.1 to 10 mM). Results: Above 1 mM, HMB decreased the extent of proliferation normally observed after stimulation by concanavalin A. The decrease was evident at 10 mM HMB, when the proliferation index was 50% reduced when compared with the absence of HMB. Cell cycle analysis demonstrated an increase in the proportion of cells at the G0-G1 phase at 10 mM HMB. CD25 and pERK1/2 expression were not related to the observed effect on proliferation. HMB affected the concentrations of all five cytokines measured following stimulation. Tumor necrosis factor-alpha concentration in the culture medium was reduced by similar to 35% at all HMB concentrations. Th1/Th2 cytokine production was modified toward a Th2 profile when HMB was at 1 or 10 mM. Thus, HMB at 10 mM impairs lymphocyte proliferation and progression through the cell cycle. The lowest concentration used here (0.1 mM) exerted some actions on cytokine production, including decreasing TNF-alpha production, but not on proliferation and cell cycle progression. Conclusion: HMB may be a useful agent to consider for modulation of immune function in specific situations. (C) 2011 Elsevier Inc. All rights reserved.