The immunomodulatory effect of oral NaHCO 3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks.

Autor: Alvarez MR; School of Graduate Studies & Department of Internal Medicine, Division of Rheumatology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA. Milena.rodriguezalvarez@downstate.edu.; Department of Rheumatology, SUNY Downstate Health Sciences University, 450 Clarkson Ave, Brooklyn, NY, 11203, USA. Milena.rodriguezalvarez@downstate.edu., Alkaissi H; Division of Diabetes, Endocrinology, and Metabolic Diseases, NIH/NIDDK, Bethesda, MD, USA., Rieger AM; Department of Medical Microbiology and Immunology, University of Alberta, Alberta, Canada., Esber GR; Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Canada., Acosta ME; Mathematics and Computer Sciences Department, Barry University, Miami, FL, USA., Stephenson SI; Division of Comparative Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA., Maurice AV; Division of Comparative Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA., Valencia LMR; Department of Anesthesiology, Downstate Health Sciences University, Brooklyn, NY, USA., Roman CA; Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA., Alarcon JM; Department of Cell Biology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2024 Mar 28; Vol. 21 (1), pp. 79. Date of Electronic Publication: 2024 Mar 28.
DOI: 10.1186/s12974-024-03067-x
Abstrakt: Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO 3 ) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO 3 -induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO 3 's immunomodulatory effects are mediated by the splenic nerve. Female rats received NaHCO 3 or water (H 2 O) for four days, and splenic immune markers were assessed using flow cytometry. NaHCO 3 led to a significant increase (p < 0.05, and/or partial eta squared > 0.06) in anti-inflammatory markers, including CD11bc + CD206 + (M2-like) macrophages, CD3 + CD4 + FoxP3 + cells (Tregs), and Tregs/M1-like ratio. Conversely, proinflammatory markers, such as CD11bc + CD38 + TNFα + (M1-like) macrophages, M1-like/M2-like ratio, and SSC high /SSC low ratio of FSC high CD11bc + cells, decreased in the spleen following NaHCO 3 administration. These effects were abolished in spleen-denervated rats, suggesting the necessity of the splenic nerve in mediating NaHCO 3 -induced immunomodulation. Artificial neural networks accurately classified NaHCO 3 and H 2 O treatment in sham rats but failed in spleen-denervated rats, highlighting the splenic nerve's critical role. Additionally, spleen denervation independently influenced Tregs, M2-like macrophages, Tregs/M1-like ratio, and CD11bc + CD38 + cells, indicating distinct effects from both surgery and treatment. Principal component analysis (PCA) further supported the separate effects. Our findings suggest that the splenic nerve transmits oral NaHCO 3 -induced immunomodulatory changes to the spleen, emphasizing NaHCO 3 's potential as an IR activator with therapeutic implications for a wide spectrum of systemic inflammatory conditions.
(© 2024. The Author(s).)
Databáze: MEDLINE
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