Everson A Nunes1, Amy R Lomax2, Paul S Noakes2, Elizabeth A Miles2, Luiz C Fernandes3, Philip C Calder2. 1. Department of Physiology, Biological Science Building, Federal University of Paraná, Curitiba-PR, Brazil. Electronic address: eanunes@ufpr.br. 2. Institute of Human Nutrition, School of Medicine, University of Southampton, Southampton, United Kingdom. 3. Department of Physiology, Biological Science Building, Federal University of Paraná, Curitiba-PR, Brazil.
Abstract
OBJECTIVE: The main objective was to investigate the potential immunomodulatory effects of β-hydroxy-β-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-α concentration in the culture medium was reduced by ~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-α 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.
OBJECTIVE: The main objective was to investigate the potential immunomodulatory effects of β-hydroxy-β-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-α concentration in the culture medium was reduced by ~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-α 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.
Authors: Chandrika J Piyathilake; Maurizio Macaluso; Ronald D Alvarez; Min Chen; Suguna Badiga; Nuzhat R Siddiqui; Jeffrey C Edberg; Edward E Partridge; Gary L Johanning Journal: Nutrition Date: 2011-05 Impact factor: 4.008