Chronic Infections and the Hypothalamus-Pituitary-Adrenal Axis in the Context of Immune-Mediated Inflammation

The immune system plays an essential role in distinguishing between self and non-self and hence protecting the host from infections. Upon the pathogen encounter, the host seeks to ensure an adequate inflammatory reaction to combat infection but at the same time tries to prevent collateral damage due to excessive immune activation. As such, limiting inflammation during an infection is an essential goal, for which several counterregulatory mechanisms are put into play, like the production of adrenal steroid hormones. This will assure a successful defense and adaptation of the organism to injury, highlighting the relevance of the relationship between adrenal hormones and the immune response. Chronic infections with bacteria, or parasites were found to display several endocrine abnormalities, ranging from subtle disturbances to substantial alterations in the regulation of the HPA axis. Facts accounting for such disturbances encompass several non-mutually exclusive possibilities, inflammation in neuroendocrine tissues, partly due to the presence of pathogens and the ensuing structural and functional alterations; along with the exploitation of the host's hormonal microenvironment by the infectious agent. Alterations in the steroid hormone axis may be also viewed as one of the consequences resulting from the re-directioning of energy to the immune system during chronic infections. Collectively, these alterations further contribute to a deficient control of infection and immunopathology, together with metabolic changes, which promote an unsuitable scenario for disease prognosis.