The effect of granulocyte macrophage-colony stimulating factor on bacterial translocation after administration of 5-fluorouracil in rats.
BACKGROUND
After surgical resection for colorectal carcinoma there is a high recurrence rate and, therefore, adjuvant chemotherapy may be useful in some patients. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent in the management of patients with colorectal cancer. However, gastrointestinal injury induced by chemotherapeutic agents may result in bacterial translocation from the gut into the systemic circulation. Granulocyte macrophage-colony stimulating factor (GM-CSF) may be used to prevent this side effect by means of macrophage activity stimulation.


METHODS
A total of 45 rats were divided into three groups. Control group received intraperitoneal saline solution, 5-FU and GM-CSF groups received 50 mg/kg/day 5-FU intravenous infusion and GM-CSF group also received 200 ng/day GM-CSF subcutaneously for 6 days. Intestinal tissue was also sampled for pathological examination at day 7. Plasma levels of tumor necrosis factor-alpha and interleukin-6 were determined, bacterial translocation was quantified by lymph node, liver and spleen culture, and plasma endotoxin content was measured.


RESULTS
White blood cell counts of the 5-FU rats were significantly lower than in the control and GM-CSF groups (P < 0.01). The plasma endotoxin, tumor necrosis factor-alpha and interleukin-6 levels in the 5-FU and GM-CSF groups were significantly increased at day 7 compared with the control groups (P < 0.01), but these levels were significantly lower in the GM-CSF group compared to the 5-FU group (P < 0.01). 5-FU intervention caused significant increase in the frequencies of bacterial translocation at liver, spleen, mesenteric lymph node, and portal blood. Compared with 5-FU group, GM-CSF decreased the bacterial translocation (P < 0.01).


CONCLUSIONS
This study observed that the administration of 5-FU resulted in bacterial translocation. Activation of inflammatory response with GM-CSF is highly effective in prevention of bacterial translocation in 5-FU interventions.
Kucuk
Can
C
Department of General Surgery, Erciyes University School of Medicine, Kayseri, Turkey. cankucuk@erciyes.edu.tr
Ozkan
Metin
M
Akgun
Hulya
H
Muhtaroglu
Sebahattin
S
Sozuer
Erdogan
E
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D018988:Bacterial Translocation / Q000187:drug effects* / Q000502:physiology; D004731:Endotoxins / Q000097:blood; D005472:Fluorouracil / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D007082:Ileum / Q000382:microbiology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D012157:Mononuclear Phagocyte System / Q000382:microbiology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000964:Antimetabolites, Antineoplastic; D004731:Endotoxins; D006133:Growth Substances; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil