title: Histamine increases anti-CD3 induced IL-5 production of TH2-type T cells via histamine H2-receptors.
abstract: Besides its proinflammatory functions histamine released from basophils and mast cells during immediate-type hypersensitivity reactions is known to inhibit several lymphocyte functions like IL-2 and gamma-IFN production. Recently, it has been shown that T helper cells of type 2 phenotype (TH2) represent the T cell fraction which may play a pivotal role in the promotion of the allergic inflammatory eosinophilic late-phase reaction by secretion of cytokines, especially IL-4 and IL-5. We have investigated the effect of histamine on anti-CD3 induced IL-4 and IL-5 production by TH2 cells. Histamine in concentrations between 10(-7) and 10(-5) mol/l concentration-dependently increased anti-CD3 induced IL-5 production up to 120%, whereas IL-4 production was not affected. The activity of histamine in increasing IL-5 production was mimicked by the H2-receptor agonist dimaprit. Histamine induced increase in IL-5 production was inhibited by histamine H2-receptor antagonists, but remained unaffected by H1- or H3-receptor antagonists. Administration of forskolin which directly stimulates the production of cAMP, the second messenger of the H2-receptor, also resulted in an increase in anti-CD3 induced IL-5 production. These results indicate that the histamine-mediated increase in anti-CD3 induced IL-5 production is mediated via H2-receptors. Consequently, histamine released from mast cells and basophils during the early-phase allergic reaction may act as an important stimulatory signal for the initiation of the allergic inflammatory late-phase reaction by increasing local IL-5 production of allergen triggered TH2 cells.
authors.affiliation: Department of Pharmacology, ASTA Medica AG, Frankfurt/Main, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
authors.forename: S
authors.initials: S
authors.lastname: Fleissner
authors.forename: I
authors.initials: I
authors.lastname: Heimann-Weitschat
authors.forename: R
authors.initials: R
authors.lastname: Lindstaedt
authors.forename: I
authors.initials: I
authors.lastname: Szelenyi
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007202:Indicators and Reagents; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D017442:Histamine Agonists; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007202:Indicators and Reagents; D015848:Interleukin-5; D011970:Receptors, Histamine H2; D005576:Colforsin; D015847:Interleukin-4; D006632:Histamine; D000242:Cyclic AMP