Prophylactic ciprofloxacin treatment prevented high mortality, and modified systemic and intestinal immune function in tumour-bearing rats receiving dose-intensive CPT-11 chemotherapy.
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.
Xue
H
H
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.
Field
C J
CJ
Sawyer
M B
MB
Dieleman
L A
LA
Baracos
V E
VE
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis / Q000379:methods*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D002939:Ciprofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced / Q000150:complications; D005260:Female; D018928:Immunity, Mucosal / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D000077146:Irinotecan; D008207:Lymphatic Metastasis; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis
D000890:Anti-Infective Agents; D000972:Antineoplastic Agents, Phytogenic; D002939:Ciprofloxacin; D000077146:Irinotecan; D002166:Camptothecin