Journal of Antimicrobial Chemotherapy (2002) 50, 51-58
© 2002 The British Society for Antimicrobial Chemotherapy
Effect of ciprofloxacin on lethal and sublethal challenge with endotoxin and on early cytokine responses in a murine in vivo model
Division of Pediatric Infectious Diseases and Immunology, Weill Medical College of Cornell University, NY, USA
Received 28 November 2001; returned 19 February 2002; revised 3 April 2002; accepted 19 April 2002
The influence of ciprofloxacin on immune responses has been suggested by results of in vitro and in vivo studies. This effect was studied using a murine model that measured mortality and early cytokine responses after challenge with endotoxin. C57/BL6 mice weighing between 18 and 21 g were given a single intraperitoneal dose of lipopolysaccharide (LPS), ranging from 200 to 1000 µg. Mice were pre-treated with an intraperitoneal injection of 5% dextrose in sterile water containing 0.0–6.0 mg of ciprofloxacin 1 h before LPS challenge. Cytokine responses were assessed by measuring concentrations in serum separated from blood obtained by cardiac puncture of anaesthetized mice at 0, 1, 3, 6 and 24 h following LPS administration. Mice were observed for 72 h following administration of LPS and serum cytokines were measured using ELISA. More than 4.5 mg of ciprofloxacin (675–900 mg/m2 or 225–300 mg/kg) given 1 h before LPS challenge consistently protected mice from a lethal dose of LPS (14/14 versus 0/7, P < 0.00001). Ciprofloxacin significantly attenuated the production of tumour necrosis factor-
and interleukin-12 response after LPS challenge. In addition, ciprofloxacin significantly increased serum interleukin-10 concentrations but had little or no effect on interleukin-6 or interleukin-1ß serum concentrations. Similar effects were evident with sublethal doses of LPS and were most pronounced at the lowest dose of LPS studied. These observations indicate that ciprofloxacin can prevent endotoxin-mediated death and alter early host cytokine responses. This effect may influence the course of infection in a manner that is independent of the drug’s antimicrobial activity.
Keywords: ciprofloxacin, fluoroquinolone, cytokine response, inflammatory response, endotoxin, mortality, innate immunity, immune response, murine, in vivo
* Correspondence address. Clinical Research, Johnson and Johnson Pharmaceutical Research and Development, Route 202, Box 300, Raritan, NJ 08869, USA. Tel: +1-908-704-4316; Fax: +1-908-595-0843; E-mail: gnoel1{at}prius.jnj.com
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