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 (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.

A novel adjuvant, a mixture of alum and the general opioid antagonist naloxone, elicits both humoral and cellular immune responses for heat-killed Salmonella typhimurium vaccine.

In the current study, we tested the efficacy of the mixture of naloxone, an opioid receptor antagonist, and alum, as a new adjuvant, in the induction of humoral and cellular immunity in response to heat-killed Salmonella typhimurium (HKST) as a model vaccine. BALB/c mice were divided into five groups. Mice in the experimental groups received either the HKST vaccine alone or in combination with the adjuvant alum, naloxone or the alum-naloxone mixture. Mice in the negative control group received phosphate-buffered saline. All mice were immunized two times on days 0 and 14. Two weeks after the last immunization, immune responses to S. typhimurium were assessed. Our results indicated that the administration of the alum-naloxone mixture as an adjuvant increased the ability of the HKST vaccine to enhance lymphocyte proliferation, shifted the immune response towards a T-helper 1 (Th1) pattern and increased S. typhimurium-specific immunoglobulin G (IgG), IgG2a, IgG1 and the ratio of IgG2a to IgG1. This resulted in improved protective immunity against S. typhimurium. In conclusion, the administration of the alum-naloxone mixture as an adjuvant, in combination with the HKST vaccine, can enhance both humoral and cellular immunity and shift the immune responses to a Th1 pattern.

Naloxone and alum synergistically augment adjuvant activities of each other in a mouse vaccine model of Salmonella typhimurium infection.

Alum is the most commonly used adjuvant for human vaccination but is a poor inducer of cell mediated immunity and T helper 1 (Th1) responses. We have previously shown that naloxone (NLX), which is a general opioid antagonist, acts as an effective adjuvant in enhancing vaccine-induced cellular immunity and Th1 immune responses. Here, we tested the efficacy of an alum-NLX mixture, as a new adjuvant, in the induction of humoral and cellular immunity in response to endotoxin-removed lysate (ERL) of Salmonella typhimurium (S. typhimurium) as a model vaccine. BALB/c mice were divided into five vaccination groups. Mice in the experimental groups received either the ERL vaccine alone or in combination with the adjuvant alum, NLX or the alum-NLX mixture. Mice in the negative control group received phosphate-buffered saline. All mice were immunized on days 0 and 7. Two weeks after the last immunization, immune responses to S. typhimurium were assessed. Our results indicate that including the alum-NLX mixture as an adjuvant during vaccination increased the ability of the ERL vaccine to enhance lymphocyte proliferation, shifted the immune response toward a Th1 profile and increased S. typhimurium-specific IgG, IgG2a and the ratio of IgG2a to IgG1. This resulted in improved protective immunity against S. typhimurium. In conclusion, administering an alum-NLX mixture adjuvant in combination with the ERL vaccine enhances both humoral and cellular immunity, and shifts the immune response to a Th1 pattern.

Evaluation of the adjuvant activity of naloxone, an opioid receptor antagonist, in combination with heat-killed Listeria monocytogenes vaccine.

We have previously demonstrated the adjuvant activity of naloxone (NLX), a general opioid antagonist, using a DNA vaccine for herpes simplex virus type 1. Here, the adjuvant activity of NLX has been evaluated using a heat-killed Listeria monocytogenes (HKLM) vaccine as a model for general immunization against intracellular bacteria. BALB/c mice were divided into three groups: the Vac group received the HKLM vaccine alone; the NLX-Vac group received the HKLM vaccine in combination with the adjuvant NLX; and the control group received phosphate buffered saline (PBS). Our results indicate that the administration of NLX as an adjuvant enhances the ability of the HKLM vaccine to increase lymphocyte proliferation, delayed type hypersensitivity, and skewing of the immune response toward a T-helper 1 (Th1) pattern. Additionally, combination of NLX with the HKLM vaccine improves protective immunity against L. monocytogenes. In conclusion, administration of NLX as an adjuvant for the HKLM vaccine can enhance cell-mediated immunity and shift the immune response to Th1.