Alterations of the hypothalamic-pituitary-adrenal axis in systemic immune diseases - a role for misguided energy regulation

Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S23-31. Epub 2011 Oct 21.


The investigation of the hypothalamicpituitary-adrenal (HPA) axis in chronic inflammation has demonstrated: 1) an anti-inflammatory influence of the HPA axis; 2) low serum levels of adrenal androgen; 3) equivocal results with respect to levels of adrenocorticotropic hormone and cortisol; 4) inadequately low secretion of adrenal hormones in relation to inflammation (the disproportion principle); 5) modulating role of TNF and IL-6 on the HPA axis; 6) disturbed cooperativity of HPA axis and sympathetic nervous system (uncoupling); 7) observable glucocorticoid resistance; 8) the circadian rhythmicity explains morning symptoms; 9) new medications based on malfunction of the HPA axis (e.g. adapted to the circadian rhythm of hormones and cytokines); and 10) the newly described role of the HPA axis in the context of misguided energy regulation in chronic inflammatory diseases. This review discusses items 1-6 and 10, while the other items are presented elsewhere in this Supplement. Evidence is presented that the basis for many alterations is in an adaptive program positively selected for short-lived inflammatory responses (energy appeal reaction), which becomes a disease-inherent pathogenetic factor, if it continues too long, that can drive systemic disease sequelae of chronic inflammatory diseases such as the metabolic syndrome.

Publication types

  • Review

MeSH terms

  • Animals
  • Energy Metabolism / immunology*
  • Humans
  • Hypothalamo-Hypophyseal System / immunology*
  • Hypothalamo-Hypophyseal System / metabolism
  • Immune System Diseases / immunology*
  • Immune System Diseases / metabolism
  • Pituitary-Adrenal System / immunology*
  • Pituitary-Adrenal System / metabolism
  • Rheumatic Diseases / immunology*
  • Rheumatic Diseases / metabolism