title: The effect of synthetic C-reactive protein on the in vitro immune response of human PBMCs stimulated with bacterial reagents.
abstract: Synthetic C-reactive protein (CRP) rescues mice from lethal endotoxin shock or bacterial infection by suppressing tumor necrosis factor (TNF-α), but in turn, enhances Kupffer cell phagocytic activity. We herein assessed the influence of CRP in human peripheral blood mononuclear cells (PBMCs). When human PBMCs were stimulated in vitro with penicillin-treated Streptococcus pyogenes, bacterial DNA motifs and lipopolysaccharide with or without synthetic CRP, CRP suppressed the production of TNF-α and IL-12, but not that of IFN-γ. This was also the case for the in vitro Shwartzman reaction induced in PBMCs. CRP also decreased high-mobility group box 1 production from macrophages, which is crucial in the later phase of endotoxin/septic shock. However, CRP upregulated the perforin expression by CD56(+) NK cells and increased their antitumor cytotoxicity. CRP may thus be a potent immunomodulatory factor in the human immune system, suggesting its therapeutic potential for use against human septic shock.
authors: Department of Immunology and microbiology, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors: Atsushi
authors: A
authors: Sato
authors: Hiroyuki
authors: H
authors: Nakashima
authors: Manabu
authors: M
authors: Kinoshita
authors: Masahiro
authors: M
authors: Nakashima
authors: Yoshiko
authors: Y
authors: Ogawa
authors: Satoshi
authors: S
authors: Shono
authors: Masami
authors: M
authors: Ikarashi
authors: Shuhji
authors: S
authors: Seki
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000494:pharmacology* / Q000627:therapeutic use; D004269:DNA, Bacterial / Q000276:immunology; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D054353:Perforin / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000188:drug therapy*; D012790:Shwartzman Phenomenon / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D004269:DNA, Bacterial; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D018664:Interleukin-12; D007371:Interferon-gamma; D002097:C-Reactive Protein