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Clinical and Diagnostic Laboratory Immunology, Sep 1995, 549-553, Vol 2, No. 5
Copyright © 1995 by the American Society for Microbiology. All rights reserved.

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, AM Isetta, G Grau, W Buurman and LJ van Tits
Pharmacological Research Institute Mario Negri, Milan, Italy.

The production of tumor necrosis factor alpha (TNF-alpha), interleukin- 1 beta (IL-1 beta), 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- alpha was detectable in serum, spleen, liver, and lungs during the first 4 h, with a peak 2 h after CLP. IL-1 beta 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 NG-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.(ABSTRACT TRUNCATED AT 250 WORDS)


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Antimicrob. Agents Chemother. Clin. Microbiol. Rev. Infect. Immun.
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Copyright © 1995 by the American Society for Microbiology. All rights reserved.