Simultaneous onset of acute inflammatory response, sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapy.
Chemotherapy is 1 method for the treatment of cancer, but serious side effects can sometimes limit the dosage given. Mild fever and diarrhea are common side effects of cancer chemotherapy. Gastrointestinal injury induced by chemotherapeutic agents may result in bacterial/endotoxin translocation from the gut into the systemic circulation. An experimental study was therefore conducted to clarify the effect of systemic chemotherapeutic agents on gastrointestinal barrier function. Male Wistar rats were divided into a 5-fluorouracil (5-FU) group (100 mg/kg/day for 4 days; n = 27) and a control group (n = 5). All rats were fasted and central venous catheterization was performed for total parenteral nutrition and blood sampling. Intestinal tissue was also sampled for pathological examination. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) were determined by ELISA, bacterial translocation was quantified by lymph node culture and plasma endotoxin content of portal blood was measured by the Limulus-amebocyte-lysate test. In the 5-FU group on day 4, a proportion of rats exhibited severe watery diarrhea (73.9%) and occasional vomiting (86.2%). The levels of plasma TNFalpha and IL-6 were seen to increase, peaking at day 6 (IL-6, 350.0 +/- 67.8 pg/ml; TNFalpha, 26.1 +/- 3.2 pg/ml). The pathological findings also changed on day 4. On day 6, 90% of the rats in the 5-FU group showed dramatic sepsis-like manifestations, whereas the control group did not. Within the 5-FU group, only at day 6 was bacterial translocation in the rat mesenteric lymph nodes or significantly elevated levels of endotoxin evident. These results suggest that bacterial/endotoxin translocation might cause sepsis-like manifestations after systemic chemotherapy.
Tsuji
Eiichi
E
Department of Surgery, University of Tokyo, Tokyo, Japan.
Hiki
Naoki
N
Nomura
Sachiyo
S
Fukushima
Ryoji
R
Kojima
Jun-ichi
J
Ogawa
Toshihisa
T
Mafune
Ken-ichi
K
Mimura
Yoshikazu
Y
Kaminishi
Michio
M
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology / Q000382:microbiology; D018988:Bacterial Translocation / Q000187:drug effects*; D004064:Digestive System / Q000187:drug effects / Q000382:microbiology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000097:blood; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010289:Parenteral Nutrition, Total; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005472:Fluorouracil