The histamine-cytokine network in allergic inflammation.
Histamine is synthesized and released by human basophils, mast cells, and neurons. Its pleiotropic effects are mediated by the activation of 4 receptors: H(1), H(2), H(3), and H(4). With the advent of selective antagonists (the antihistamines widely used to treat allergic disorders), the H(1)-receptor was the first member of the receptor family to be pharmacologically defined. Increasing evidence indicates that, in addition to exerting immediate vascular and bronchial responses, histamine might modulate the immune reaction by interacting with T cells, macrophages, basophils, eosinophils, and monocytes. We have shown that, in vitro, histamine induces a concentration-dependent release of IL-6 and beta-glucuronidase from macrophages isolated from the human lung parenchyma. These effects are inhibited by fexofenadine, an H(1)-receptor antagonist, but not by ranitidine, an H(2)-receptor antagonist. This observation raises the possibility that long-term treatment with fexofenadine might have beneficial effects on immune dysregulation and tissue damage/remodeling associated with histamine-mediated macrophage activation.
Marone
Gianni
G
Division of Clinical Immunology and Allergy, University of Naples Federico II, School of Medicine, Naples, Italy.
Granata
Francescopaolo
F
Spadaro
Giuseppe
G
Genovese
Arturo
A
Triggiani
Massimo
M
D000818:Animals; D016207:Cytokines / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006632:Histamine / Q000276:immunology* / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000276:immunology / Q000627:therapeutic use; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D007107:Immune System / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*
D016207:Cytokines; D006634:Histamine H1 Antagonists; D006632:Histamine