Effects of granulocyte-colony stimulating factor on peritoneal defense mechanisms and bacterial translocation after administration of systemic chemotherapy in rats

Abstract

activity of peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. G-CSF increased both bactericidal activity of the peritoneal fluid and phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid, and prevented the bacterial translocation. We conclude that intraperitoneal GCSF administration protects the effects of systemic 5-FU on peritoneal defense mechanisms. INTRODUCTIONChemotherapy is one of the most important methods in the therapy of malignant diseases. It has been widely used and it is well known that systemic chemotherapy has immunosuppressive effects [1] . 5-Fluorouracil (5-FU) has side effects, including leucopoenia, stomatitis, appetite loss, diarrhea, and mild fever like other chemotherapy agents [2,3] . It has been reported that a high dose of 5-FU often induces cytotoxicity in intestinal tissue that results in ulceration, diarrhea, and bacterial translocation [4][5][6][7][8] .Bacterial translocation is one of the most important causes of sepsis and multiple organ failure. Intestinal mucosa has a barrier function that prevents the colonization of the bacteria and the passage of bacteria and their toxins from the intestinal system into the systemic circulation. It has been shown that bacterial translocation is also augmented by shock, mesenteric ischemia, thermal injury, malnutrition, obstructive jaundice, and intestinal obstruction [9][10][11][12][13][14] . Granulocyte-colony stimulating factor (G-CSF) is a cytokine that is used to reverse the neutropenia associated with cytotoxic chemotherapy bone marrow and haemopoietic stem cell transplantation [15] . Abstract AIM: To investigate the effects of granulocyte-colony stimulating factor (G-CSF) on peritoneal defense mechanisms and bacterial translocation after systemic 5-Fluorouracil (5-FU) administration.

Inflammation and neural signaling

“…The ability of CCAs to trigger inflammation is likely due in part to the cytotoxic action of these agents on tumor and healthy cells as dead and dying cells liberate a number of cell products that serve as ‘danger signals’ to prime resident tissue macrophages via activation of their surface Toll-like receptors (TLRs) [6]. Macrophage priming via TLR activation would likely occur following bacterial translocation (passage of bacteria or bacterial products across the intestinal mucosal barrier) related to drug-induced gastrointestinal damage [7,8]. These primed macrophages upregulate IL-1 β gene expression via activation of the stress response proteins p38, JNK, and NF-κB.…”

The role of IL-1β and TNF-α signaling in the genesis of cancer treatment related symptoms (CTRS): A study using cytokine receptor-deficient mice

“…In addition, priming of these cells via TLR activation also occurs following bacterial translocation (passage of bacteria or bacterial products i.e. endotoxin, across the intestinal mucosal barrier) related to chemotherapy induced gastrointestinal damage [11,12]. In addition to these indirect effects, cytotoxic chemotherapy directly increase the synthesis and release of IL-1β from macrophages via activation of the mitogen activated protein 3 kinase (MAP3K) ZAK and formation of the NLRP3 inflammasome [13,14].…”

Bacterial Translocation in Alymphoplasia (<I>aly</I>/<I>aly</I>) Mice

“…Unlike these overt pathogens, the role of Peyer's patches in BTL of non-pathogenic indigenous bacteria is not clear and is controversial. There have been several reports that some immunosuppressants and chemotherapeutics induce BTL of indigenous bacteria in laboratory animals or human patients, because of host immunosuppression (BERG 1983;BALZAN et al 2007;CERCI et al 2007;KOH et al 2005;PENN et al 1991). However, SUZUKI et al (1996 and NAKAYAMA et al (1997) report that treatment with cyclophosphamide, one of the immunosuppressants and chemotherapeutics, reduced BTL of E. coli in mice because of the decrease and/or damage of M cells and macrophages of Peyer's patches.…”