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Clinical and Diagnostic Laboratory Immunology, Sep 1995, 549-553, Vol 2, No. 5
P Villa, G Sartor, M Angelini, M Sironi, M Conni, P Gnocchi, AM Isetta, G Grau, W Buurman and LJ van Tits
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)
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
Pharmacological Research Institute Mario Negri, Milan, Italy.
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