title: A key regulatory role for histamine in experimental autoimmune encephalomyelitis: disease exacerbation in histidine decarboxylase-deficient mice.
abstract: Histamine can modulate the cytokine network and influence Th1 and Th2 balance and Ab-isotype switching. Thus, pharmacological blockade or genetic deletion of specific histamine receptors has been shown to reduce the severity of experimental autoimmune encephalomyelitis (EAE), a prototypic Th1-mediated disease with similarities to human multiple sclerosis. To study the comprehensive contribution of endogenous histamine to the expression of EAE, we attempted to induce EAE in histidine decarboxylase-deficient mice, which are genetically unable to make histamine. In this study, we show that EAE is significantly more severe in HDC-/-, histamine-deficient mice, with diffuse inflammatory infiltrates, including a prevalent granulocytic component, in the brain and cerebellum. Unlike splenocytes from wild-type mice, splenocytes from HDC-/- mice do not produce histamine in response to the myelin Ag, whereas production of IFN-gamma, TNF, and leptin are increased in HDC-/- splenocytes in comparison to those from wild-type mice. Endogenous histamine thus appears to regulate importantly the autoimmune response against myelin and the expression of EAE, in this model, and to limit immune damage to the CNS. Understanding which receptor(s) for histamine is/are involved in regulating autoimmunity against the CNS might help in the development of new strategies of treatment for EAE and multiple sclerosis.
authors.affiliation: Immunology and Muscular Pathology Unit, National Neurological Institute "C. Besta," Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Musio
authors.forename: Barbara
authors.initials: B
authors.lastname: Gallo
authors.forename: Stefano
authors.initials: S
authors.lastname: Scabeni
authors.forename: Marilena
authors.initials: M
authors.lastname: Lapilla
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Poliani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
authors.forename: Rosetta
authors.initials: R
authors.lastname: Pedotti
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology; D006632:Histamine; D006640:Histidine Decarboxylase / Q000172:deficiency*; D007371:Interferon-gamma / Q000096:biosynthesis; D020738:Leptin / Q000096:biosynthesis; D051379:Mice; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D006023:Glycoproteins; D020738:Leptin; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C445081:myelin oligodendrocyte glycoprotein (35-55); D006632:Histamine; D007371:Interferon-gamma; D006640:Histidine Decarboxylase