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

BackgroundSystemic inflammatory response induced by over expressing inflammatory mediators is the main pathogenic mechanism of septic shock. Glutamine (Gln) has been demonstrated to inhibit pro-inflammatory cytokine release through enhanced heat shock protein (HSP) expression.ObjectiveTo assess the effect of co-administration of Gln and antibiotic ciprofloxacin in reduction of septic shock severity caused by Pseudomonas aeruginosa in mice.MethodsSix- 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 (−), Gln, 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 500λ phosphate buffer saline (PBS). Gln group received 500λ Ala-Gln, Cip group received 500λ ciprofloxacin. The Cip + Gln group received 500λ Gln and ciprofloxacin. Finally serum TNF-α, IL-10 and HSP-70 concentrations were measured and the severity of liver necrosis was examined.ResultsGlutamine in combination with ciprofloxacin significantly increased survival rate and serum HSP-70 and IL-10 concentration and significantly decreased serum TNF-α concentration and the liver necrosis severity in comparison to control (+) group.ConclusionGln has synergistic effects with ciprofloxacin in reduction of P. aeruginosa-induced septic shock.

► Glutamine is a HSP inducer and Ciprofloxacin is an antibiotic. ► Their synergistic effects on reduction of septic shock severity were studied. ► Their co-administration reduced P. aeruginosa-induced septic shock severity.