As humans age their ability to combat bacterial infection declines and reduced immunity is further compromised at times of emotional and physical stress. Adrenocortical hormones are elevated in response to chronic stress in both young and old, but the quality of the response is dramatically altered with aging. The adrenal steroid dehydroepiandrosterone sulphate (DHEAS) is immune enhancing, while cortisol is immune suppressing. Serum DHEAS levels decline with age but cortisol does not, a process termed the adrenopause, resulting in a relative excess of the immunosuppressive hormone cortisol. Physical trauma, further increases cortisol and may increase susceptibility to infection.
In recent years we have investigated the effects of hip-fracture on cortisol:DHEAS ratios, infection susceptibility and neutrophil function in elderly humans. Our early data showed that neutrophil phagocytic ability towards both yeast and E.coli was compromised in healthy elderly subjects1. In a study of 35 elderly hip-fracture patients and 9 young subjects with limb fractures, we found that a significant number of the elderly patients (13) developed infections in the 2 months following trauma, which were mainly chest and urinary tract infections. No infections were seen in the young cohort. Serum cortisol:DHEAS ratio were measured and were significantly higher in elderly compared to young patients (P<0.0001). The cortisol:DHEAS ratio was also higher in elderly patients that succumbed to infection (P<0.02) compared to those that did not. Neutrophil superoxide generation was reduced in the elderly and in vitro cortisol inhibited neutrophil superoxide generation, an effect that was blocked by DHEAS2. Thus the response to trauma is increased in the elderly leading to suppression of neutrophil function and increased susceptibility to bacterial infections.
We have also investigated the molecular basis of the effects of DHEAS on neutrophil superoxide generation and revealed that this effect may be mediated via the activation of the Protein kinase C signalling pathway.
1. Butcher SK, Chahal H, Nayak L, Sinclair A, Henriquez NV, Sapey E, OMahony D & Lord JM. Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J. Leuk. Biol. 2001 70 881886.
2. Butcher SK, Killampalli V, Lascelles D, Wang K, Alpar EK & Lord JM. Raised cortisol:DHEAS ratios in the elderly after injury:potential impact upon neutrophil function and immunity. Aging Cell 2005 4 319324.