The protective effects of the
hormones androstenediol (androstene-3beta, 17beta,-diol; AED) and
dehydroepiandrosterone (5-androsten-3beta-
ol-17-one;
DHEA) on the pathophysiology of two lethal
bacterial infections and
endotoxin shock were examined. The
infections included a gram-positive organism (Enterococcus faecalis) and a gram-negative organism (Pseudomonas aeruginosa). Both
hormones protected mice from the lethal
bacterial infections and from
lipopolysaccharide (LPS) challenge. Treatment of animals lethally infected with P. aeruginosa with
DHEA resulted in a 43% protection whereas treatment with AED gave a 67% protection. Both
hormones also protected completely animals infected with an LD50 dose of E. faecalis. Similarly, the 88% mortality rate seen in LPS challenge was reduced to 17% and 8.5%, by treatment with
DHEA and AED, respectively. The protective influences of both
steroids were shown not to be directly antibacterial, but primarily an indirect
antitoxin reaction.
DHEA appears to mediate its protective effect by a mechanism that blocks the toxin-induced production of pathophysiological levels of tumour
necrosis factor-alpha (
TNF-alpha) and
interleukin-1. AED usually had greater protective effects than
DHEA; however, the AED effect was independent of
TNF-alpha suppression, both in vivo and in vitro. The data suggest that both
DHEA and AED may have a role in the neuro-endocrine regulation of antibacterial immune resistance.