Histamine H1-receptor antagonists with immunomodulating activities: potential use for modulating T helper type 1 (Th1)/Th2 cytokine imbalance and inflammatory responses in allergic diseases.
Being a first-line treatment for hypersensitivity allergic disease, histamine H1-receptor antagonists possess anti-inflammatory activity in addition to being H1-receptor antagonists. While it is not purely a histamine-related condition, hypersensitivity allergic disease is associated with an increase in the number of T helper type 2 (Th2) cells and Th2 cytokines, and a decrease in the number of Th1 cells and Th1 cytokines. Suppression of Th2-type cytokine production in addition to H1-receptor blockade may therefore represent a successful therapeutic strategy for the treatment of hypersensitivity allergic diseases. H1-receptor antagonists have been reported to modulate immune cascade at various points by acting on T cell-related inflammatory molecules, including adhesion molecules, chemokines and inflammatory cytokines. These effects of H1-receptor antagonists may be optimized for the treatment of allergic diseases. Besides their ability to regulate inflammatory molecules, some H1-receptor antagonists have been reported to down-regulate Th2 cytokine production. In particular, it has been shown that several H1-receptor antagonists specifically inhibit the production of Th2, but not Th1, cytokines. Accumulating evidence indicates a crucial role for Th1/Th2 cytokine imbalance on the development of allergic diseases. Accordingly, the use of H1-receptor antagonist with Th2 cytokine inhibitory activity to modulate Th1/Th2 cytokine imbalance might be a favourable strategy for the treatment of hypersensitivity allergic diseases. Furthermore, the identification of H1-receptor antagonists which possess immunoregulatory activities in addition to their anti-histamine activity will provide an important insight into the development of novel immunoregulatory drugs.
Okamoto
T
T
Division of Clinical Immunology, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Iwata
S
S
Ohnuma
K
K
Dang
N H
NH
Morimoto
C
C
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007155:Immunologic Factors / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D006680:HLA Antigens; D006634:Histamine H1 Antagonists; D007155:Immunologic Factors