Bacterial translocation is downregulated by anti-TNF-alpha monoclonal antibody administration in rats with cirrhosis and ascites.
OBJECTIVE
TNF-alpha is involved in the development of bacterial translocation in rats with cirrhosis. The aim of the current study was to evaluate the effect of anti-TNF-alpha mAb treatment on the incidence of bacterial translocation and systemic infections in rats with cirrhosis and ascites.


METHODS
Thirty rats with cirrhosis and ascites were randomly assigned to receive two intraperitoneal doses of anti-TNF-alpha mAb, distilled water or immunoglobulin on days 0 and 4. On day 10, a laparotomy was performed.


RESULTS
One out of 11 animals receiving anti-TNF-alpha mAb treatment, 7 out of 10 of the placebo group (p<0.01), and 5 out of 9 of the IgG group developed bacterial translocation (p<0.05). A significantly reduced number of systemic infections were observed in animals receiving anti TNF-alpha mAb treatment vs animals receiving placebo (p<0.01). TNF-alpha in serum at laparotomy in animals receiving anti-TNF-alpha mAb was higher than that in the rest of groups and was also higher in the overall series of animals showing bacterial translocation.


CONCLUSIONS
In the experimental model of CCl(4)-induced rat with cirrhosis and ascitic fluid, anti-TNF-alpha mAb administration decreases the incidence of bacterial translocation, in a TNF-alpha/sTNF-alpha receptor-independent manner, without increasing the risk of systemic infections.
Francés
Rubén
R
CIBER HEPAD, Instituto de Salud Carlos III, Madrid, Spain.
Chiva
Maite
M
Sánchez
Elisabet
E
González-Navajas
José M
JM
Llovet
Teresa
T
Zapater
Pedro
P
Soriano
Germán
G
Muñoz
Carlos
C
Balanzó
Joaquín
J
Pérez-Mateo
Miguel
M
Song
Xiao-yu
XY
Guarner
Carlos
C
Such
José
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001202:Ascitic Fluid / Q000382:microbiology; D018988:Bacterial Translocation / Q000187:drug effects* / Q000276:immunology; D002251:Carbon Tetrachloride; D004195:Disease Models, Animal; D015536:Down-Regulation; D007274:Injections, Intraperitoneal; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D010538:Peritonitis / Q000382:microbiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000382:microbiology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride