[The effect of some drugs on the levels of selected cytokines in experimental septic shock].
The production of tumor necrosis factor (TNF-alpha), and interleukin 1 beta (IL-1 beta), IL-6, sTNFR-p55, sTNFR-p75 and their pharmacomodulation were evaluated in a model of septic shock induced in CD-1 mice by cecal ligation and puncture (CLP). This model of sepsis, which resembles the clinical situation of bowel perforation and peritonitis with subsequent septic shock was compared with that induced by administration of pure endotoxin (LPS). TNF-alpha was detectable in serum, liver, spleen 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. sTNFR-p55 and p75 increased in both models of shock but with different kinetics. Cytokines were also detectable after LPS injection, with kinetics similar to those after CLP but a significantly higher level. Pretreatment with dexamethasone (DEX) and ibuprofen (IBU), significantly reduced survival, while TNF did not affect it. Only pentoxifylline (PTX) significantly increased survival in mice with CLP. However DEX protected the mice from LPS mortality. In conclusion, by inhibiting TNF-alpha with DEX and PTX survival was reduced or unchanged respectively, suggesting that the modulation of this cytokine does not play significant role in sepsis and septic shock induced by CLP, unlike treatment with LPS. The negative effects of IBU suggests a protective role by prostaglandins in sepsis induced by LPS.
Ladny
J R
JR
Kliniki Chirurgii Ogólnej, Akademii Medycznej w Białymstoku.
Dzienis
H
H
Dadan
J
J
Polaków
J
J
Venskutonis
D
D
Puchalski
Z
Z
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D007052:Ibuprofen / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010431:Pentoxifylline / Q000494:pharmacology; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D015996:Survival Rate
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003907:Dexamethasone; D010431:Pentoxifylline; D007052:Ibuprofen