Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity

The protective effects of the hormones androstenediol (androstene-3 beta, 1 7 beta,-diol; AED) and dehydroepiandrosterone (5-androsten-3 beta-ol-17-one ; DHEA) on the pathophysiology of two lethal bacterial infections and endot oxin shock were examined. The infections included a gram-positive organism (Enterococcus faecalis) and a gram-negative organism (Pseudomonas aeruginos a). Both hormones protected mice from the lethal bacterial infections and f rom lipopolysaccharide (LPS) challenge, Treatment of animals lethally infec ted with P. aeruginosa with DHEA resulted in a 43% protection whereas treat ment with AED gave a 67% protection, Both hormones also protected completel y animals infected with an LD50 dose of E, faecalis, Similarly, the 88% mor tality rate seen in LPS challenge was reduced to 17% and 8.5%, by treatment with DHEA and AED, respectively, The protective influences of both steroid s were shown not to be directly antibacterial, but primarily an indirect an titoxin reaction. DHEA appears to mediate its protective effect by a mechan ism that blocks the toxin-induced production of pathopysiological levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1, AED usually ha d greater protective effects than DHEA; however, the AED effect was indepen dent 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.