title: Experimental allergic encephalomyelitis is inhibited in transgenic mice expressing human C-reactive protein.
abstract: We show here using a transgenic model that human C-reactive protein (CRP) protects against experimental allergic encephalomyelitis (EAE) in C57BL/6 mice. In transgenic compared with wild-type females, the duration of the human CRP acute phase response that accompanies the inductive phase of active EAE correlates with a delay in disease onset. In transgenic males, which have higher human CRP expression than females do, EAE is delayed, and its severity is reduced relative to same-sex controls. Furthermore, in male transgenics, there is little or no infiltration of the spinal cord by CD3(+) T cells and CD11b(+) monocytes and macrophages, and EAE is sometimes prevented altogether. CRP transgenics also resist EAE induced passively by transfer of encephalitogenic T cells from wild-type donors. Human CRP has three effects on cultured encephalitogenic cells that could contribute to the protective effect observed in vivo: 1) CRP inhibits encephalitogenic peptide-induced proliferation of T cells; 2) CRP inhibits production of inflammatory cytokines (TNF-alpha, IFN-gamma) and chemokines (macrophage-inflammatory protein-1alpha, RANTES, monocyte chemoattractant protein-1); and 3) CRP increases IL-10 production. All three of these actions are realized in vitro only in the presence of high concentrations of human CRP. The combined data suggest that during the acute phase of inflammation accompanying EAE, the high level of circulating human CRP that is achieved in CRP-transgenic mice inhibits the damaging action of inflammatory cells and/or T cells that otherwise support onset and development of EAE.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, AL 35294, USA. Alex.Szalai@ccc.uab.edu
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szalai
authors.forename: Serge
authors.initials: S
authors.lastname: Nataf
authors.forename: Xian-Zhen
authors.initials: XZ
authors.lastname: Hu
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000502:physiology*; D054407:Chemokine CCL4; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005260:Female; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D054407:Chemokine CCL4; C571326:MOG protein, human; D019402:Macrophage Inflammatory Proteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein