Vipera aspis venom reduces lethality and down-regulates tumor necrosis factor-alpha in a rat model of LPS-induced sepsis.
OBJECTIVE
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-alpha and IL-1beta. 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-alpha 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-alpha 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.
Frolkis
Inna
I
Department of Cardiothoracic Surgery, Tel Aviv-Sourasky Medical Center, Tel Aviv University, Israel.
Klein
Yifat
Y
Locker
Chaim
C
Adi
Nimrod
N
Dahan
Esther
E
Uretzsky
Gideon
G
Shapira
Itzhak
I
Sorkine
Patrick
P
D000818:Animals; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000139:chemically induced* / Q000276:immunology / Q000401:mortality; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014757:Viper Venoms / Q000378:metabolism*; D017819:Viperidae
D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014757:Viper Venoms