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Adrenergic mechanisms in infection. III. alpha-and beta-receptor blocking agents in treatment
Abstract:
Raised epinephrine concentrations concentrations developed in the blood of mice near death after an intraperitoneal challenge with 10(9) Staphylococcus aureus or Escherichia coli. Both epinephrine levels were elevated in the urine near death. These challenges were infections and not intoxications, as they could be successfully treated with antibiotics. Using the same model infections, we studied the effect of alpha-and beta-receptor blocking agents and other adrenergically active compounds. The compounds alone were not toxic in the doses used. alpha-Blockers, such as phenoxybenzamine, dibenamine, and ergotamine and beta-blockers, such as butoxamine, timolol, and practolol, were ineffective. Phentolamine alone or propranolol alone showed some evidence of an ability to prolong life in S. aureus infections. Together they lengthened life significantly in S. aureus-challenged mice. In E. coli infections this beneficial effect was not noted. Mice pretreated with reserpine (7 mg/kg) and challenged with S. aureus lived 55% longer than saline-treated controls. Less benefit was noted in E. coli infections. Serontonin treatment was helpful in S. aureus infections and deleterious in E. coli infections.
Insights
Bacterial infections increase epinephrine levels in dying mice. Combined alpha- and beta-blockers prolonged survival in Staphylococcus aureus infections, but not E. coli infections, suggesting a role for adrenergic pathways in sepsis.
Area of Science:
- Microbiology
- Pharmacology
- Immunology
Background:
- Bacterial infections, such as those caused by Staphylococcus aureus and Escherichia coli, can lead to significant physiological stress.
- Elevated epinephrine levels have been observed in critically ill patients and animal models, but their role in sepsis survival is not fully understood.
Purpose of the Study:
- To investigate the effect of adrenergic receptor blockade on survival during bacterial infections.
- To explore the potential of adrenergically active compounds in modulating the host response to sepsis.
Main Methods:
- Mice were intraperitoneally challenged with Staphylococcus aureus or Escherichia coli.
- Various alpha- and beta-adrenergic blocking agents, as well as reserpine and serotonin, were administered.
- Survival rates were monitored to assess the efficacy of the treatments.
Main Results:
- Epinephrine levels increased in the blood and urine of mice near death from S. aureus or E. coli infections.
- Combined administration of phentolamine (alpha-blocker) and propranolol (beta-blocker) significantly prolonged survival in S. aureus-infected mice.
- Reserpine pretreatment extended survival in S. aureus infections, while serotonin showed a beneficial effect in S. aureus but a detrimental effect in E. coli infections.
Conclusions:
- Adrenergic pathways play a role in the host response to S. aureus infections.
- Combination alpha- and beta-adrenergic blockade may offer a therapeutic strategy for certain bacterial infections.
- The differential effects of reserpine and serotonin highlight the complexity of modulating host responses in sepsis.