The Effect of Synthetic C-Reactive Protein on the In Vitro Immune Response of Human PBMCs Stimulated

Abstract—Synthetic C-reactive protein (CRP) rescues mice from lethal endotoxin shock or bacte-rial 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 mononu-clear cells (PBMCs). When human PBMCs were stimulated in vitro with penicillin-treated Strept-ococcus 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. KEY WORDS: inflammation; C-reactive protein; tumor necrosis factor-α; high-mobility group box 1; human PBMCs