Vipera aspis venom reduces lethality and down-regulates tumor necrosis factor-α in a rat model of LPS-induced sepsis

Inna Frolkis, Yifat Klein, Chaim Locker, Nimrod Adi, Esther Dahan, Gideon Uretzsky, Itzhak Shapira, Patrick Sorkine

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Sepsis and septic shock are major causes of morbidity and mortality in critically-ill patients. Sepsis constitutes the systemic response to infection, that is predominantly mediated by the pro-inflammatory cytokines TNF-α and IL-1β. Hence, cytokine modulation provides a promising target for the treatment of sepsis. In this work we evaluated the effect of a low-dose Vipera aspis venom (VAV) vaccine on survival and cytokine serum levels in a rat model of lipopolysaccharide (LPS)-induced septic shock. Methods: Adult male Wistar rats were given either VAV vaccine or saline, and 2 weeks later half of each group received LPS challenge, and were monitored for mortality, cytokine levels, blood count and chemistry. Results: Survival rate was significantly higher in venom-treated, compared to non-vaccinated septic rats. Furthermore, VAV treatment significantly reduced LPS-associated TNF-α and LDH, without affecting IL-6 and IL-10 levels, and modified WBC and platelet counts. Conclusions: Our data suggest that sub-toxic doses of VAV have a protective effect against LPS-induced septic shock that may be mediated, at least partially, by the modulated TNF-α activity. This study thus offers a novel therapeutic approach for the attenuation of bacteremia-induced septic shock through the modulation of a central pro-inflammatory cytokine by VAV vaccination in mammals.

Original languageEnglish
Pages (from-to)319-324
Number of pages6
JournalCytokine
Volume49
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • Septic shock
  • TNF-α
  • Vipera aspis venom (VAV)

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