Pattern of cytokines and pharmacomodulation in sepsis induced by cecal ligation and puncture compared with that induced by endotoxin

P. Villa, G. Sartor, M. Angelini, M. Sironi, M. Conni, P. Gnocchi, A. M. Isetta, G. Grau, W. Buurman, L. J H Van Titts, P. Ghezzi

Research output: Contribution to journalArticlepeer-review

Abstract

The production of tumor necrosis factor alpha (TNF-α) interleukin-1β (IL-1β), and IL-6 and their pharmacomodulation were evaluated in a model of polymicrobial sepsis induced in mice by cecal ligation and puncture (CLP) and were compared with the effects of endotoxin (lipopolysaccharide [LPS] treatment. LPS levels rose as early as 1 h after CLP and increased further after 2 and 21 h. TNF-α was detectable in serum, spleen, liver, and lungs during the first 4 h, with a peak 2 h after CLP. IL-1β was measurable in serum after 24 h, and levels increased significantly in spleen and liver 4 and 8 h after CLP. IL-6 levels Increased significantly in serum throughout the first 16 h after CLP. These cytokines were detectable after LPS injection, with kinetics similar to those after CLP but at a significantly higher level. To cast more light on the differences between these two animal models of septic shock, we studied the effects of different reference drugs. Pretreatment with dexamethasone (DEX); ibuprofen (IBU), an inhibitor of cyclooxygenase; and N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthase, significantly reduced survival while chlorpromazine (CPZ) and TNF did not affect it. Only the antibiotics and pentoxifylline significantly increased survival in mice with CLP. However, CPZ and DEX protected the mice from LPS mortality on inhibiting. TNF-α with DEX, CPZ, or pentoxifylline, survival was reduced, unchanged, and increased, respectively, and on increasing TN-α with IBU and TNF, survival was decreased or unchanged, respectively, suggesting that the modulation of this cytokine does not play a significant role in sepsis induced by CLP, unlike treatment with LPS. The negative effects of IBU and NG-nitro-L-arginine suggest a protective role by prostaglandins and nitric oxide In sepsis induced by CLP.

Original languageEnglish
Pages (from-to)549-553
Number of pages5
JournalClinical and Diagnostic Laboratory Immunology
Volume2
Issue number5
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

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