Sickness behaviour pushed too far – the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma

Certain distinctive components of the severe systemic inflammatory syndrome are now well-recognized to be common to malaria, sepsis, viral infections, and post-trauma illness. While their connection with cytokines has been appreciated for some time, the constellation of changes that comprise the syndrome has simply been accepted as an empirical observation, with no theory to explain why they should coexist. New data on the effects of the main pro-inflammatory cytokines on the genetic control of sickness behaviour can be extended to provide a rationale for why this syndrome contains many of its accustomed components, such as reversible encephalopathy, gene silencing, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia. It is thus proposed that the pattern of pathology that comprises much of the systemic inflammatory syndrome occurs when one of the usually advantageous roles of pro-inflammatory cytokines – generating sickness behaviour by moderately repressing genes (Dbp, Tef, Hlf, Per1, Per2 and Per3, and the nuclear receptor Rev-erbα) that control circadian rhythm – becomes excessive. Although reversible encephalopathy and gene silencing are severe events with potentially fatal consequences, they can be viewed as having survival advantages through lowering energy demand. In contrast, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia may best be viewed as unfortunate consequences of extreme repression of these same genetic controls when the pro-inflammatory cytokines that cause sickness behaviour are produced excessively. As well as casting a new light on the previously unrationalized coexistence of these aspects of systemic inflammatory diseases, this concept is consistent with the case for a primary role for inflammatory cytokines in their pathogenesis across this range of diseases

Declines in sexual activity and function predict incident health problems in older adults: prospective findings from the English Longitudinal Study of Ageing

The objective of this study was to investigate cross-sectional and longitudinal associations between declines in sexual activity and function and health outcomes in a large population-based sample of older adults. Data were from 2577 men and 3195 women aged ≥ 50 years participating in the English Longitudinal Study of Ageing. Past-year changes in sexual desire, frequency of sexual activity, and ability to have an erection (men)/become sexually aroused (women) were assessed at baseline by self-completion questionnaire. Health outcomes (self-rated health, limiting long-standing illness, doctor-diagnosed diseases of the vascular system, and cancer) were self-reported at baseline (2012/2013) and 4-year follow-up (2016/2017). Data were analyzed using logistic regression, adjusted for sociodemographics, health behaviors, and depressive symptoms. Prospectively, men who reported a decline in sexual desire had higher odds of incident limiting long-standing illness (OR 1.41, 95% CI 1.04–1.91) and incident cancer (OR 1.63, 95% CI 1.06–2.50) than those who maintained their sexual desire. Men who reported a decline in the frequency of sexual activities had higher odds of deterioration in self-rated health (OR 1.47, 95% CI 1.04–2.08) and incident limiting long-standing illness (OR 1.69, 95% CI 1.20–2.37). In women, a decline in frequency of sexual activities was associated with deterioration of self-rated health (OR 1.64, 95% CI 1.07–2.51). Erectile dysfunction was longitudinally associated with poorer health outcomes including incident cancer (OR 1.73, 95% CI 1.11–2.70), coronary heart disease (OR 2.29, 95% CI 1.29–4.07), and fair/poor self-rated health (OR 1.66, 95% CI 1.19–2.32). Practitioners should be mindful that a decline in sexual activity, desire, or function in older age may be an important indicator of future adverse health outcomes