Table 4.
In vitro studies on human samples evaluating the beneficial effects of BT on immune response in inflammatory diseases
| Authors | Journal | Treatment | Experimental model | Mineral water or inorganic or organic components | Pathology | Biochemicalparameters | Results |
|---|---|---|---|---|---|---|---|
| Rinaldi et al. 2006 [27] | Lab Investig | 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 ↓ caspase-3 cleavage and p38/MAPK phosphorylation in neutrophils Accelerate the resolution of inflammatory processes |
| Mirandola et al. 2007 [28] | J Cell Physiol |
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 |
↓ proliferation of lymphocyte subsets ↓ D8 + T and NK cells ↓ IL-2 production Accelerate the resolution of inflammatory processes |
| Sulen et al. 2016 [29] | Pharmacol Res | 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 |
↑ p38/MAPK, Akt, and CREB phosphorylation ↓ inflammatory processes |
| Han et al. 2013 [30] | Cell Physiol Biochem | 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 |
↑ cell proliferation and S phase distribution of cell cycle ↓ Akt (ser473), GSK (ser9) ↑ p27Kip1 and p21CIP1 expression and phosphorylation ↓ inflammatory processes |
| Braga et al. 2008 [31] | Respiration |
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 |
↓ ROS and RNS release at 0.94 to 15.5 μg/mL of HS ↓ inflammatoryprocesses |
| Braga et al. 2010 [32] | TherAdvRespirDis | 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 (AcquiTerme, Piemonte, Italy) and NaHS | Inflammatory processes of upper and lower airway diseases | Elastase release; elastolyticactivity |
Inhibited elastase release ↓ inflammatory processes |
| Prandelli et al. 2013 [23] | Int J ImmunopatholPharmacol |
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 |
↓ TNF-α, IL-1β, IL-6, IL-12, CXCL8, CCL5 production ↓ ROS formation and antioxidant enzymes Sirmione water ↑ IL-10 release ↓ chronic inflammatory and age-related illness manifestations |
| Vitale 2018 [34] | Bol Soc Esp Hidrol Méd | Exogenous H2S on human resting CD4 T cell polarization to Th17 and/or Treg phenotype | Differentiated ex-vivo human resting CD4 + (Th0) T cells to Th17 or Treg lineages | NaHS | Immune-mediated pathologies | CD4 T cell polarization to Th17 and/or Treg phenotype |
↑ Foxp3 mRNA levels in CD4 + T cells cultured under Treg-polarizing conditions ↑ RORγT mRNA levels in CD4 + T cells under Th17 polarizing conditions |
AKT protein-chinasi B, CCL5 C–C motif chemokine ligand 5, CREB cAMP-response element-binding protein, CXCL8 C-X-C motif chemokine ligand 8, GSK3β glycogen synthase kinase 3 beta, HS sulfhydryl, IL interleukin, LPS lipopolysaccharide, MAPK mitogen-activated protein kinase, NaHS sodium hydrosulfide, NF-κB nuclear factor kappa B, NK natural killer, RNS reactive nitrogen species, ROS reactive oxygen species, Th T helper, TNF tumor necrosis factor, Treg regulatory T, ↓ decrease, ↑ increase