| James Michael Howard 2005-11-23, 10:58 am |
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I first produced they hypothesis that cortisol evolved to antagonize the
effects of DHEA in 1985. I suggest this is the basis of the "fight or
flight" mechanism and I realized at the time that excessive cortisol over
extended periods will adversely affect all tissues. James Michael Howard
www.anthropogeny.com
Aging Cell. 2005 Dec;4(6):319-24.
Raised cortisol:DHEAS ratios in the elderly after injury: potential impact
upon neutrophil function and immunity.
Butcher SK, Killampalli V, Lascelles D, Wang K, Alpar EK, Lord JM.
MRC Centre for Immune Regulation, Birmingham university Medical School,
Birmingham B15 2TT, UK.
Summary The detrimental effect of stress on the immune response increases
with age, though the mechanisms responsible are not fully understood. The
physiological response to stress is regulated in part by the adrenocortical
system. Adrenal hormones dehydroepiandrosterone sulphate (DHEAS) and
cortisol have opposing effects on the innate immune system, DHEAS enhances
while cortisol suppresses immunity and the molar ratio of cortisol to DHEAS
increases with age. We found that elderly hip fracture patients produced a
robust neutrophilia after injury, but circulating neutrophils showed an
impaired antibacterial response. We therefore proposed that adrenocortical
hormones mediate the heightened immunosuppression seen in the elderly after
injury. We examined neutrophil function and adrenocortical hormone levels
in elderly (> 65 years) hip fracture patients and age-matched healthy
controls. Thirteen out of 35 elderly patients acquired infections following
hip fracture. Neutrophil superoxide production was lower in elderly hip
fracture patients compared with controls (P < 0.005) and lower in patients
who acquired infection following injury compared with those who did not (P
< 0.05). Serum cortisol:DHEAS ratio was higher in elderly hip fracture
patients (0.56 +/- 0.38) compared with either age-matched controls (0.36
+/- 0.21; P < 0.05) or young fracture patients (0.087 +/- 0.033; P <
0.0001). Moreover, cortisol: DHEAS was increased in elderly patients who
succumbed to infection compared with those who did not (0.803 +/- 0.42 vs.
0.467 +/- 0.28; P < 0.02). In vitro cortisol significantly decreased
neutrophil superoxide generation (P < 0.05) and this was prevented by
coincubation with DHEAS. We propose that increased cortisol:DHEAS ratios
may contribute to reduced immunity following physical stress in the
elderly.
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