Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation.

Mast cells (MCs) are derived from hematopoietic progenitors, mature in vascularized tissues, and participate in innate and acquired immunity. Neuroinflammation is a highly debated topic in the biomedical literature; however, the impact of tumor necrosis factor (TNF) and IL-33 on MCs in the brain has not been widely addressed. MCs can be activated by IgE binding to FcεRI, as well as by different antigens. After activation, MCs mediate various immunological and inflammatory responses through TNF and IL-33. TNF has two receptors: TNFR1, a p55 molecule, and TNFR2, a p75 molecule. This cytokine is the only one of its kind to be stored in the granules of MCs and can also be generated by de novo synthesis via mRNA. In the central nervous system (CNS), TNF is produced almost exclusively by microglial cells, neurons, astrocytes, and, minimally, by endothelial cells. After its release into brain tissue, TNF rapidly induces the adhesion molecules endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells. TNF causes the chemoattraction of neutrophils by inducing several molecules, including CXC chemokines (IL-8). Both MCs and microglial cells act as a primary barrier against foreign molecules in the CNS, producing pro-inflammatory cytokines such as IL-33. IL-33 belongs to the IL-1 family, is activated through the ST2L/IL1-RAcP receptor complex, and mediates both the innate and adaptive immune response. IL-33 is a nuclear transcription factor expressed in the brain, where it induces pro-inflammatory cytokines (TNF and IL-1) and chemokines (CCL2, CCL3, CCL5, and CXCL10). Therefore, MCs and microglia in the CNS are a source of pro-inflammatory cytokines, including TNF and IL-33, that mediate many brain diseases. The inhibition of TNF and IL-33 may represent a new therapeutic approach that could complement existing neuroinflammatory therapies.

IL-37 evaluation in chronic periodontitis after periodontal treatment with and without low level laser therapy.

BACKGROUND: Periodontal disease poses a significant global health challenge. Traditional treatments focus on reducing inflammation and bacterial load, yet novel approaches are continually being investigated. Recent research suggests that IL-37, a potent anti-inflammatory cytokine, may play a crucial role in modulating the inflammatory processes associated with periodontal disease. In conjunction with IL-37, low-level laser therapy (LLLT) has gained attention for its potential in promoting tissue repair, reducing inflammation, and enhancing cellular processes. This study aims to investigate the effects of LLLT on IL-37 in periodontal disease management. METHODS: Thirty patients were enrolled: the G1 group patients were treated with only scaling and root planning-SRP, the G2 group was treated with SRP and LLLT. Before treatment (T0) all periodontal probing pocket depth and bleeding on probing were obtained. Before (T0) and 10 (T1), 30 (T2) and 60 (T3) days after treatment, was achieved plaque sample and specimens of gingival crevicular fluid. Diode laser wavelength range was used between 600-1000 nm and 0.04-60 J/cm2 energy density for 3-s spotlights. RESULTS: In all patients PPD, BOP and IL-37 have shown healing improved parameters. CONCLUSIONS: Although LLLT is widely recommended for its biostimulatory and anti-inflammatory roles, it only showed additional short-term merits in reducing the pocket depth after conventional SRP. Its long-term adjunctive benefits remain unclear. Future RCTs with better study designs, adequate sample power and longer durations of follow-up are required to assess the effectiveness of LLLT as an adjunctive treatment strategy in patients with periodontal disease.