Glucocorticoid Regulates NLRP3 in Acute-On-Chronic Hepatitis B Liver Failure

Int J Med Sci. 2019 Mar 9;16(3):461-469. doi: 10.7150/ijms.30424. eCollection 2019.

Abstract

Acute-on-chronic hepatitis B liver failure (ACHBLF) refers to the acute deterioration of liver function during chronic hepatitis B virus infection, and is associated with high mortality, with rapid progression to death. Nucleotide-binding oligomerisation domain-like receptors (NLRs) Family Pyrin Domain Containing 3(NLRP3) inflammasome contributed to the pathogenesis of D-galactosamine and lipopolysaccharide-induced acute liver failure. However, the profile of NLRP3 in patients with ACHBLF has not been demonstrated. This study was therefore conducted to investigate the expression of NLRP3 in patients with ACHBLF and identify the effect of glucocorticoid on NLRP3. We recruited 70 patients with ACHBLF undergoing glucocorticoid treatment for 28 days, 30 patients with chronic hepatitis B (CHB), and 24 healthy controls (HCs) in this study. The relative messenger RNA (mRNA) level of NLRP3 and related genes were measured by reverse transcription polymerase chain reaction, the plasma levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. The mRNA level of NLRP3 was significantly higher in patients with ACHBLF than in patients with CHB as well as HCs (P<0.05). The plasma levels of IL-1β and IL-18 in patients with ACHBLF were significantly higher than in patients with CHB and HCs (P<0.05). The relative mRNA level of NLRP3 in surviving patients decreased significantly compared with that in patients who did not survive after glucocorticoid treatment (P<0.05). In conclusion, NLRP3 increased in patients with ACHBLF. Glucocorticoid could downregulate the expression of NLRP3 in surviving patients with ACHBLF.

Keywords: ACHBLF; NLRP3; glucocorticoid treatment.

MeSH terms

  • Acute-On-Chronic Liver Failure / drug therapy
  • Acute-On-Chronic Liver Failure / etiology*
  • Acute-On-Chronic Liver Failure / mortality
  • Adult
  • Female
  • Gene Expression Regulation / drug effects
  • Glucocorticoids / therapeutic use*
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / metabolism
  • Humans
  • Interleukin-18 / blood
  • Interleukin-1beta / blood
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein / blood
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • Prednisolone / therapeutic use

Substances

  • Glucocorticoids
  • IL18 protein, human
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Prednisolone
  • Methylprednisolone