The Interplay Between Antigen-Induced Mast Cell Activation, Histamine Release and Cyclooxygenase Enzyme Activity in the Pathogenesis of Fever: A Comprehensive Review

Fever represents a complex physiological response orchestrated by multiple cellular and molecular mechanisms within the immune system. This comprehensive review examines the intricate relationships between antigen-induced mast cell activation, histamine release, and cyclooxygenase (COX) enzyme activity in fever pathogenesis. Mast cells, strategically positioned throughout tissues, serve as sentinel cells that respond to antigenic stimuli through rapid degranulation and mediator release. The subsequent cascade involves histamine-mediated vascular changes and the activation of COX enzymes, particularly COX-2, leading to prostaglandin E2 (PGE2) synthesis and hypothalamic thermoregulatory responses. Current evidence demonstrates that these pathways are interconnected through complex feedback mechanisms involving inflammatory cytokines, complement activation, and neuroimmune signalling. Understanding these molecular interactions provides critical insights for developing targeted therapeutic interventions. This review synthesizes current literature to elucidate the mechanistic basis of fever development and identifies potential therapeutic targets for clinical management.