Prophylactic ciprofloxacin treatment prevented high mortality, and modified systemic and intestinal immune function in tumour-bearing rats receiving dose-intensive CPT-11 chemotherapy

Br J Cancer. 2009 May 19;100(10):1581-8. doi: 10.1038/sj.bjc.6605051. Epub 2009 Apr 28.


Infectious complications are a major cause of morbidity and mortality from dose-intensive cancer chemotherapy. In spite of the importance of intestinal bacteria translocation in these infections, information about the effect of high-dose chemotherapy on gut mucosal immunity is minimal. We studied prophylactic ciprofloxacin (Cipro) treatment on irinotecan (CPT-11) toxicity and host immunity in rats bearing Ward colon tumour. Cipro abolished chemotherapy-related mortality, which was 45% in animals that were not treated with Cipro. Although Cipro reduced body weight loss and muscle wasting, it was unable to prevent severe late-onset diarrhoea. Seven days after CPT-11, splenocytes were unable to proliferate (stimulation index=0.10+/-0.02) and produce proliferative and inflammatory cytokines (i.e., Interleukin (IL)-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) IL-1beta, IL-6) on mitogen stimulation in vitro (P<0.05 vs controls), whereas mesenteric lymph node (MLN) cells showed a hyper-proliferative response and a hyper-production of pro-inflammatory cytokines on mitogen stimulation. This suggests compartmentalised effects by CPT-11 chemotherapy on systemic and intestinal immunity. Cipro normalised the hyper-responsiveness of MLN cells, and in the spleen, it partially restored the proliferative response and normalised depressed production of IL-1beta and IL-6. Taken together, Cipro prevented infectious challenges associated with immune hypo-responsiveness in systemic immune compartments, and it may also alleviate excessive pro-inflammatory responses mediating local gut injury.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / therapeutic use
  • Antibiotic Prophylaxis / methods*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Carcinoma / drug therapy*
  • Carcinoma / immunology
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Ciprofloxacin / pharmacology
  • Ciprofloxacin / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Diarrhea / chemically induced
  • Diarrhea / complications
  • Female
  • Immunity, Mucosal / drug effects*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Irinotecan
  • Lymphatic Metastasis
  • Neoplasm Transplantation
  • Rats
  • Rats, Inbred F344
  • Spleen / drug effects
  • Spleen / pathology
  • Survival Analysis


  • Anti-Infective Agents
  • Antineoplastic Agents, Phytogenic
  • Ciprofloxacin
  • Irinotecan
  • Camptothecin