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

Abstract

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 index0.10±0.02) and produce proliferative and inflammatory cytokines (i.e., Interleukin (IL)-2, interferon- (IFN-), tumour necrosis factor-α (TNF-α) IL-1Β, 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-1Β 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. © 2009 Cancer Research UK.