Histamine regulation of interleukin-18-initiating cytokine cascade is associated with down-regulation of intercellular adhesion molecule-1 expression in human peripheral blood mononuclear cells.
In the previous study, we demonstrated that interleukin (IL)-18 up-regulated intercellular adhesion molecule-1 (ICAM-1) expression on monocytes in human peripheral blood mononuclear cells (PBMC) and that heterotypic interaction between monocytes/T or NK cells through ICAM-1/LFA-1 intensified the production of IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) in PBMC. In the present study, we demonstrate that histamine inhibited the ICAM-1 expression in monocytes induced by IL-18 using flow cytometry and that the responses of IL-12, IFN-gamma, and TNF-alpha induced by IL-18 were concentration dependently inhibited by coexisting histamine, whereas IL-18-inhibited IL-10 production was reversed by the same concentrations of histamine. The modulatory effects of histamine on ICAM-1 expression and cytokine production were all concentration dependently antagonized by famotidine but not by d-chlorpheniramine and thioperamide, and were mimicked by selective H(2)-receptor agonists but not by H(1)- and H(3)-receptor agonists, indicating the involvement of H(2)-receptors in histamine action. The inhibition of IL-18-induced IFN-gamma by histamine was ascribed to the strong inhibition of IL-12 production by histamine. Histamine thus operates the negative feedback mechanism against IL-18-activated cytokine cascade through the strong inhibitory effect on ICAM-1 expression and IL-12 production in monocytes, contributing to the formation of diverse pattern of cytokine activation from Th1 to Th2, depending on the monocyte/macrophage activation and cytokine environment.
Takahashi
Hideo Kohka
HK
Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Yoshida
Atsushi
A
Iwagaki
Hiromi
H
Yoshino
Tadashi
T
Itoh
Hideyuki
H
Morichika
Toshihiko
T
Yokoyama
Minori
M
Akagi
Tadaatsu
T
Tanaka
Noriaki
N
Mori
Shuji
S
Nishibori
Masahiro
M
D002449:Cell Aggregation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D005434:Flow Cytometry; D006632:Histamine / Q000502:physiology*; D017442:Histamine Agonists / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000187:drug effects
D016207:Cytokines; D017442:Histamine Agonists; D007202:Indicators and Reagents; D020382:Interleukin-18; D011970:Receptors, Histamine H2; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine