Sickness behavior of rats with abdominal sepsis can be improved by antibiotic and G-CSF prophylaxis in clinic modeling randomized trials.
OBJECTIVE
In clinical sepsis research nearly all immune-modulators have demonstrated no benefit in regard to the 28-day mortality rate. Other endpoints such as quality of life have become more attractive, but clinically relevant animal models analyzing an equivalent to quality of life by measurement of sickness behavior are extremely rare. The concept of clinic modeling randomized trials was used in an animal trial to model clinical complexity and conditions of a randomized clinical trial.


METHODS
80 adult male Wistar rats were randomly assigned to (1) control: anesthesia and sham operation, (2) sepsis: laparotomy and peritoneal infection with human stool bacteria, (3) sepsis with antibiotic prophylaxis: cefuroxime/metronidazole and (4) sepsis with antibiotic plus a cytokine prophylaxis with granulocyte-colony stimulating factor (GCSF). Endpoints were physiological and behavioral parameters.


RESULTS
The combination of antibiotics plus G-CSF was most effective in reducing mortality. All infected animals showed reduced open field activity acutely after infection, and recovery was improved during the 9 day follow-up in rats with prophylactic treatments. In the social interaction test, but not in the elevated plus-maze anxiety test, prophylaxis was also efficient, especially with antibiotics and G-CSF.


CONCLUSIONS
The results show that improving sickness behavior in septic rats with G-CSF plus antibiotics may be a promising approach.
Bauhofer
A
A
Institute of Theoretical Surgery, Philipps-University of Marburg, Baldingerstrasse, 35033 Marburg, Germany. bauhofer@staff.uni-marburg.de
Schwarting
R K W
RK
Köster
M
M
Schmitt
A
A
Lorenz
W
W
Pawlak
C R
CR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology*; D015996:Survival Rate
D000900:Anti-Bacterial Agents; D016179:Granulocyte Colony-Stimulating Factor