Abstract
Summary
Group A streptococcal pyrogenic exotoxin type C (SPE C) was shown to produce fever which in part depended upon norepinephrine and stimulation of α-adrenergic receptors. Intracisternal injection of norepinephrine into rabbits already showing fevers due to SPE C resulted in further heightened fevers. Pretreatment of animals with either α-methyl tyrosine to deplete norepinephrine stores or phenoxybenzamine to block α-receptors depressed SPE-induced pyrogenicity. Pretreatment of animals with P-chlorophenylalanine to deplete serotonin stores accentuated fevers due to SPE and giving serotonin intracisternally to rabbits with fevers resulted in a significant drop in body temperature. This indicated serotonin exerted a negative effect on SPE pyrogenicity. Isoproterenol and propranolol did not affect SPE C fever production. When used alone, none of the drugs prevented the capacity of SPE C to enhance lethal endotoxin shock. However, phenoxybenzamine in combination with fluid replacement increased the survival rate of rabbits. It is proposed that SPE C may alter the endotoxin detoxification system, thus allowing endotoxin to persist in the circulation producing shock.
This work was supported by USPHS Grant AI-06487 from the National Institute of Allergy and Infectious Diseases. Dr. Schlievert received stipend support from USPHS Training Grant HLI-07014 from the National Heart, Lung and Blood Institute.
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