Simultaneous inhibition of three major cytokines and its therapeutic effects: A peptide-based novel therapy against endotoxemia in mice

Hung Jen Shih, Chao Yuan Chang, Milton Chiang, Van Long Le, Hao Jen Hsu, Chun Jen Huang

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Three major cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, mediate endotoxemia-induced liver injury. With the similar structures to the binding do-mains of the three cytokines to their cognate receptors, the novel peptide KCF18 can simultaneously inhibit TNF-α, IL-1β, and IL-6. We elucidated whether KCF18 can alleviate injury of liver in endotox-emic mice. Adult male mice (BALB/cJ) were intraperitoneally (i.p.) administered lipopolysaccharide (LPS, 15 mg/kg; LPS group) or LPS with KCF18 (LKCF group). Mice in the LKCF group received KCF18 (i.p.) at 2 h (0.6 mg/kg), 4 h (0.3 mg/kg), 6 h (0.3 mg/kg), and 8 h (0.3mg/kg) after LPS administration. Mice were sacrificed after receiving LPS for 24 h. Our results indicated that the binding levels of the three cytokines to their cognate receptors in liver tissues in the LKCF group were significantly lower than those in the LPS group (all p <0.05). The liver injury level, as measured by performing functional and histological analyses and by determining the tissue water content and vascular permeability (all p <0.05), was significantly lower in the LKCF group than in the LPS group. Similarly, the levels of inflammation (macrophage activation, cytokine upregulation, and leukocyte infiltration), oxidation, necroptosis, pyroptosis, and apoptosis (all p < 0.05) in liver tissues in the LKCF group were significantly lower than those in the LPS group. In conclusion, the KCF18 peptide–based simultaneous inhibition of TNF-α, IL-1β, and IL-6 can alleviate liver injury in mice with endotoxemia.

Original languageEnglish
Article number436
JournalJournal of Personalized Medicine
Volume11
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords

  • Apoptosis
  • IL-1β
  • IL-6
  • Liver
  • Necroptosis
  • Pyroptosis
  • TNF-α

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Fingerprint

Dive into the research topics of 'Simultaneous inhibition of three major cytokines and its therapeutic effects: A peptide-based novel therapy against endotoxemia in mice'. Together they form a unique fingerprint.

Cite this