Table 3.

In vitro studies on human and animal samples evaluating the beneficial effects of BT on immune response

Authors	Treatment(s)	Experimental model	Mineral water or inorganic or organic components	Pathology	Biochemical parameters	Results
(Rinaldi et al. 2006)	NaHS (from 0.23 to 3.66 mM) dissolved in the culture medium, for 24 h + p38/MAPK inhibitors (30–60 μM)	Human purified neutrophils, eosinophils or lymphocytes	NaHS	Inflammatory processes of respiratory tract	Cell viability and apoptosis; P38/MAPK signaling activation/deactivation	Short-term survival of neutrophils delaying the onset of apoptosis Reduced caspase-3 cleavage and p38/MAPK phosphorylation in neutrophils Accelerate the resolution of inflammatory processes
(Mirandola et al. 2007)	NaHS (from 0.20 to 4.0 mM) dissolved in the culture medium, for 24 h + caspase inhibitors (30 μM)	Human purified peripheral blood lymphocytes	NaHS	Inflammatory processes	Cell viability and apoptosis; IL-2	Decreased proliferation of lymphocyte subsets, CD8+ T and NK cells, and reduced IL-2 production Accelerate the resolution of inflammatory processes
(Sulen et al. 2016)	NaHS (10, 100 or 1000 μM) dissolved in the culture medium, for 10 min	Human peripheral blood mononuclear cells (PBMCs)	NaHS	Inflammatory processes	p38/MAPK, NF-κB p65, AKT and CREB phosphorylation	Induced p38/MAPK, AKT, and CREB phosphorylation Reduction of inflammatory processes
(Miller et al. 2012)	H2S (50–500 nM) dissolved in the culture medium, for 4, 10, and 24 h	Primary mouse T lymphocytes (CD3+), OT-II CD4+ T cells	H2S	Inflammatory processes of bowel diseases	CD69, CD25; IL-2; cystathionine γ-lyase, cystathionine β-synthase	Enhanced T cell activation, CD69, and IL-2 expression, and CD25 levels; Increased cystathionine γ-lyase and cystathionine β-synthase expression Reduction of inflammatory processes of bowel diseases
(Han et al. 2013)	NaHS (0.25, 0.5, 1, 2, 4 and 8 mM) and GYY4137 (200, 400, 800, 1600 μM) dissolved in the culture medium, for 0.5, 1, 2, 4, 6, 12, 24, 36, 48 h	Human purified peripheral blood lymphocytes	NaHS and GYY4137	Inflammatory processes of systemic lupus erythematosus	Cell viability, cell cycle distribution; AKT (ser473), GSK3β (ser9), p27Kip1 and p21CIP1	Increased cell proliferation and S phase distribution of cell cycle; Decreased AKT (ser473), GSK (ser9), and increased p27Kip1 and p21CIP1 expression and phosphorylation Reduction of inflammatory processes of systemic lupus erythematosus
(Braga et al. 2008)	Sulfurous thermal water (different concentrations) dissolved in the culture medium, for 15 min + N-formyl-methionyl-leucyl-phenylalanine/phorbol-12-myristate-13-acetate	Human purified neutrophils	Sulfurous thermal water (Acqui Terme, Piemonte, Italy), which contains different HS groups concentrations	Inflammatory processes	ROS and RNS	Reduced ROS and RNS release at 0.94 to 15.5 μg/mL of HS Reduction of inflammatory processes
(Braga et al. 2010)	Sulfurous water or NaHS (from 4.5 to 18 mg/mL) dissolved in the culture medium, for 15 min	Human purified neutrophils	Sulfurous thermal water (Acqui Terme, Piemonte, Italy) and NaHS	Inflammatory processes of upper and lower airway diseases	Elastase release; elastolytic activity	Inhibited elastase release Reduction of inflammatory processes
(Prandelli et al. 2013)	Sirmione thermal water or NaHS (2.5 mM) dissolved in the culture medium, for 24 h + LPS 100 (ng/mL)	Human primary monocytes	Sirmione thermal water (Lombardia, Italy), rich in sodium chloride, bromine and iodine	Chronic inflammatory and age-related illness	TNF-α, IL-1β, IL-6, IL-12; CXCL8, CCL5; ROS, antioxidant enzymes	NaHS reduced TNF-α, IL-1β, IL-6, IL-12, CXCL8, CCL5 production, ROS formation and antioxidant enzymes; Sirmione water enhanced IL-10 release Reduction of chronic inflammatory and age-related illness manifestations

NaHS natrium hydrogen sulfide, MAPK mitogen-activated protein kinase, IL interleukin, NK natural killers, H₂S hydrogen sulfide, CD3 cluster of differentiation 3, CD4 cluster of differentiation 4, CD69 cluster of differentiation 69, CD25 interleukin-2 receptor alpha chain, GYY4137 exogenous slow releasing H₂S, Akt protein kinase B, GSK3β glycogen synthase kinase-3β, p27^Kip1 cyclin-dependent kinase inhibitor 1B, p21^CIP1 cyclin-dependent kinase inhibitor 1, PBMCs human peripheral blood mononuclear cells, NF-κB nuclear factor-κB, CREB cAMP response element-binding protein, ROS reactive oxygen species, RNS reactive nitrogen species, LPS lipopolysaccharide, TNF-α tumor necrosis factor α, CXCL8 chemokine (C-X-C motif) ligand 8, CCL5 Chemokine (C-C motif) ligand 5