Synergistic effects of glutamine and ciprofloxacin in reduction of Pseudomonas aeruginosa-induced septic shock severity

Background: Systemic inflammatory response induced by over expressing inflammatory mediators is the main pathogenic mechanism of septic shock. Glutamine (Gin) has been demonstrated to inhibit pro-inflammatory cytokine release through enhanced heat shock protein (HSP) expression. Objective: To assess the effect of co-administration of GIn and antibiotic ciprofloxacin in reduction of septic shock severity caused by Pseudomonas aeruginosa in mice. Methods: Six- to eight-week old male BALB/c mice were used. At first, P. aeruginosa susceptibility to ciprofloxacin was determined. Then, 75% lethal dose (LD 75) of P. aeruginosa in a 10-day period was assessed. For determining survival rate, fifty mice were divided into 5 groups which included control (+), control (-), GIn, ciprofloxacin, and "glutamine + ciprofloxacin" group. All mice, except for control (-), were given an LD75 dose of P. aeruginosa and after 30 min each group received its special treatment: control (-) and control (+) groups received only 500 lambda phosphate buffer saline (PBS). GIn group received 500 lambda AIa-GIn, Cip group received 500 lambda ciprofloxacin. The Cip + GIn group received 500 lambda GIn and ciprofloxacin. Finally serum TNF-alpha, IL-10 and HSP-70 concentrations were measured and the severity of liver necrosis was examined. Results: Glutamine in combination with ciprofloxacin significantly increased survival rate and serum HSP-70 and IL-10 concentration and significantly decreased serum TNF-a concentration and the liver necrosis severity in comparison to control (+) group. Results: Glutamine in combination with ciprofloxacin significantly increased survival rate and serum HSP-70 and IL-10 concentration and significantly decreased serum TNF-alpha concentration and the liver necrosis severity in comparison to control (+) group. Conclusion: GIn has synergistic effects with ciprofloxacin in reduction of P. aeruginosa-induced septic shock. (C) 2011 Elsevier B.V. All rights reserved.