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Alvarez, M. R., Alarcon, J. M., & Roman, C. A. (2023). Can a basic solution activate the inflammatory reflex? A review of potential mechanisms, opportunities, and challenges. Pharmacological Research, 187, 106525. Added by: Dr. Enrique Feoli (26/06/2025, 18:50) Last edited by: Dr. Enrique Feoli (26/06/2025, 18:53) |
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| Resource type: Journal Article DOI: 10.1016/j.phrs.2022.106525 ID no. (ISBN etc.): 1043-6618 BibTeX citation key: Alvarez2023 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Inflammatory reflex Keywords: Cholinergic splenic anti-inflammatory pathway (CSAP), Inflammatory reflex (IR), Inflammatory reflex activators, Monocyte polarization, Sodium bicarbonate, Splanchnic anti-inflammatory pathways (SAP), Splenic nerve, Systemic inflammation, Vagal nerve stimulation (VNS) Creators: Alarcon, Alvarez, Roman Collection: Pharmacological Research |
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| Abstract |
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Stimulation of the inflammatory reflex (IR) is a promising strategy to treat systemic inflammatory disorders. However, this strategy is hindered by the cost and side effects of traditional IR activators. Recently, oral intake of sodium bicarbonate (NaHCO3) has been suggested to activate the IR, providing a safe and inexpensive alternative. Critically, the mechanisms whereby NaHCO3 might achieve this effect and more broadly the pathways underlying the IR remain poorly understood. Here, we argue that the recognition of NaHCO3 as a potential IR activator presents exciting clinical and research opportunities. To aid this quest, we provide an integrative review of our current knowledge of the neural and cellular pathways mediating the IR and discuss the status of physiological models of IR activation. From this vantage point, we derive testable hypotheses on potential mechanisms whereby NaHCO3 might stimulate the IR and compare NaHCO3 with classic IR activators. Elucidation of these mechanisms will help determine the therapeutic value of NaHCO3 as an IR activator and provide new insights into the IR circuitry.
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| Notes |
Splenic anti-inflammatory cellular mechanisms. (A) Apical splenic nerve stimulation engages cholinergic (purple dashed line) and adrenergic (orange dashed lines) fibers. Upon release, ACh and NE bind, respectively, to α7nAChR (in orange) and βA2R (in purple) on macrophages. This suppresses the production of TNFα during endotoxemia via two parallel mechanisms acting simultaneously. (B) Upon arterial splenic nerve stimulation, NE binds to ChAT+ T cells, which in turn release ACh. Ach acts on α7nAChR-expressing monocytes (in orange), inducing an anti-inflammatory polarization. ACh can also bind to α9nAChR-expressing B cells (in green), increasing T-dependent antibody formation. (C) NE release after (apical or arterial) splenic nerve stimulation act on βA2R located on splenic stromal cells. βA2R activation induces the release of the chemokine CCL13, which regulates the migration of ChAT+ T/B cells in the spleen. βA2R further modulate the expression of CCR2 on monocytes—the most important chemokine receptor during inflammation. (D) Mesothelial cells (in yellow) binding to the spleen capsule. Upon changes in the peritoneal environment, ChAT+ mesothelial cells release ACh, resulting in equivalent effects to arterial splenic stimulation (B). Figure created by Ilse Anton (@science_illustrated_by_ilse) |