Activation of Mast Cells by Neuropeptides: The Role of Pro-inflammatory and Anti-Inflammatory Cytokines

Abstract

Mass cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in scientific literature and is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptides and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

The emerging role of IL‐38 in diseases: A comprehensive review

“…IL-38 is reported to regulate the development of autoimmune diseases by inactivating immune cells and inflammatory responses through various mechanisms. 55,56 For example, IL-38 can inhibit the release of inflammatory cytokines and chemotaxis to inactivate inflammatory cells. Meanwhile, IL-38 promotes the activity of regulatory T cells (Treg) to suppress autoimmune responses.…”

The viral hypothesis in Alzheimer’s disease: SARS-CoV-2 on the cusp

“…COVID-19 patients with advanced age and comorbidities with an inflammatory basis (e.g., diabetes, atherosclerosis, and subclinical dementia) may be at increased risk of AD. Therefore, neuroinflammation caused by COVID-19 may be unmanageable, especially in older adults, because their immune system responds less efficiently (Kritas et al, 2020;Schirinzi et al, 2021).…”

Emerging functions and therapeutic targets of IL‐38 in central nervous system diseases

“…[7][8][9][10][11][12][13] Of further note, IL-36 receptor antagonist (IL-36Rα) and IL-38, two anti-inflammatory cytokines with similar functions in IL-1F reduced neuronal death and improved cognitive function defects by down-regulating the expression levels of IL-1β, tumor necrosis factor α (TNFα), and IL-6. 14,15 Therefore, targeting inflammatory cytokines is a promising new therapy for the treatment of CNS diseases and injuries. IL-38 is a newly discovered cytokine in the IL-1 family and plays an important role in a variety of diseases, including but not limited to CNS diseases.…”

“…After effective anti‐inflammatory treatment, the expression levels of these cytokines were remarkably reduced, and cognitive dysfunction was effectively improved 7–13 . Of further note, IL‐36 receptor antagonist (IL‐36Rα) and IL‐38, two anti‐inflammatory cytokines with similar functions in IL‐1F reduced neuronal death and improved cognitive function defects by down‐regulating the expression levels of IL‐1β, tumor necrosis factor α (TNF‐α), and IL‐6 14,15 . Therefore, targeting inflammatory cytokines is a promising new therapy for the treatment of CNS diseases and injuries.…”