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

Int Immunopharmacol. 2011 Dec;11(12):2214-9. doi: 10.1016/j.intimp.2011.10.003. Epub 2011 Oct 19.

Abstract

Background: Systemic 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.

Objective: To assess the effect of co-administration of Gln 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 (-), 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.

Results: Glutamine 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.

Conclusion: Gln has synergistic effects with ciprofloxacin in reduction of P. aeruginosa-induced septic shock.

MeSH terms

  • Animals
  • Ciprofloxacin / therapeutic use*
  • Drug Synergism
  • Drug Therapy, Combination
  • Glutamine / therapeutic use*
  • HSP70 Heat-Shock Proteins / blood
  • Interleukin-10 / blood
  • Liver Cirrhosis, Experimental / drug therapy
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas aeruginosa / drug effects*
  • Severity of Illness Index
  • Shock, Septic / drug therapy*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • HSP70 Heat-Shock Proteins
  • IL10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Glutamine
  • Interleukin-10
  • Ciprofloxacin