Activated Mast Cells: What Happens?

Dr. Theoharis Theoharides explains that mast cells, immune sentinels located in virtually every tissue, can be activated through many pathways—not just classic allergen/IgE signaling. They carry over 300 receptors responsive to allergens, infections, pollutants, drugs, foods, neuropeptides, and hormones. When triggered, mast cells can release mediators either all at once (degranulation) or gradually (piecemeal release), affecting every organ system and producing widespread, shifting symptoms (e.g., flushing, hives, GI upset, brain fog, tachycardia, pain). Stress hormones like corticotropin-releasing hormone (CRH) further prime and amplify mast cell responses, helping explain why stress can worsen reactivity and why some people develop sensitivity to many chemicals. This biology underpins mast cell activation syndrome and overlaps with multiple chemical sensitivity, emphasizing the importance of identifying triggers and recognizing the multi-system nature of symptoms.