The article explores the impact of tumor necrosis factor (TNF) and interleukin-33 (IL-33) cytokines on mast cells (MCs) in neuroinflammation. MCs, derived from hematopoietic progenitors, play a crucial role in innate and acquired immunity. They can be activated by IgE binding to FcεRI and various antigens, leading to the production of pro-inflammatory cytokines such as TNF and IL-33. TNF, which is stored in MC granules and can be synthesized de novo, acts through two receptors, TNFR1 and TNFR2, and induces the expression of adhesion molecules and chemokines, contributing to neutrophil recruitment and inflammation. IL-33, a member of the IL-1 family, activates MCs through the ST2L/IL1-RAcP receptor complex, promoting Th2 cytokines and chemokines. Both TNF and IL-33 are involved in various neurological diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and Multiple Sclerosis (MS). The article highlights the potential therapeutic benefits of inhibiting these cytokines, particularly in the context of neuroinflammatory disorders.The article explores the impact of tumor necrosis factor (TNF) and interleukin-33 (IL-33) cytokines on mast cells (MCs) in neuroinflammation. MCs, derived from hematopoietic progenitors, play a crucial role in innate and acquired immunity. They can be activated by IgE binding to FcεRI and various antigens, leading to the production of pro-inflammatory cytokines such as TNF and IL-33. TNF, which is stored in MC granules and can be synthesized de novo, acts through two receptors, TNFR1 and TNFR2, and induces the expression of adhesion molecules and chemokines, contributing to neutrophil recruitment and inflammation. IL-33, a member of the IL-1 family, activates MCs through the ST2L/IL1-RAcP receptor complex, promoting Th2 cytokines and chemokines. Both TNF and IL-33 are involved in various neurological diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and Multiple Sclerosis (MS). The article highlights the potential therapeutic benefits of inhibiting these cytokines, particularly in the context of neuroinflammatory disorders.