The effects of histamine on interferon gamma production are dependent on the stimulatory signals

• Published in: International immunopharmacology 2001, Vol.1 (1), p.135-145
• Main Authors: Osna, Natalia, Elliott, Kathleen, Khan, Manzoor M
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bucladesine - pharmacology; CD3 antigen; Clone Cells; Cyclic AMP-Dependent Protein Kinase Type II; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - metabolism; Enzyme Inhibitors - pharmacology; g-Interferon; Histamine; Histamine - pharmacology; Histamine H1 Antagonists - pharmacology; Immunomodulators; In Vitro Techniques; Interferon gamma; Interferon-gamma - biosynthesis; Lymphocyte Activation; Medical sciences; Mice; Mice, Inbred AKR; Mice, Inbred DBA; Murine TH1 cloned cells; Pharmacology. Drug treatments; Protein kinase A; Splenocytes; Th1 Cells - drug effects; Th1 Cells - enzymology; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - enzymology; Th2 Cells - immunology
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/S1567-5769(00)00005-9

Histamine regulates the immune response by enhancing TH2 cytokine production and by inhibiting TH1 cytokine production. We assessed the mechanisms of histamine's action on helper T cell subsets by evaluating the role of protein kinase A (PKA) in the histamine-mediated effects on IFNγ production. The splenocytes and TH1 murine cloned cells (pGL10) were pretreated with histamine at a concentration range of 10 −8–10 −5 M for 1 h and then were activated with anti-CD3, PHA, PMA+ionomycin, or ionomycin for 24 h. The levels of IFNγ were measured in the supernatants by ELISA. The inhibitory effects of histamine were the most prominent in anti-CD3-stimulated splenocytes (61%). The effects of histamine on IFNγ production from TH1 cells depended on the mode of cell activation. The activation of cells with anti-CD3 resulted in 27% inhibition of IFNγ production whereas the activation with ionomycin produced 70% suppression. The inhibitory effects of histamine were completely reversed by cimetidine in a dose-dependent manner in both TH1 cells and in splenocytes. PKA played a role in the inhibition of IFNγ by histamine when the cells were activated via TCR, and the PKA inhibitors Rp-cAMPS (10 −5 M) and H8 (10 −5 M) reversed the inhibitory effects of histamine on IFNγ production. However, when the cells were stimulated with ionomycin, the PKA inhibitors did not affect histamine-mediated suppression of IFNγ production.