Minireview: Neuro-immuno-endocrine modulation of the hypothalamic-pituitary-adrenal (HPA) axis by gp130 signaling molecules

Endocrinology. 2002 May;143(5):1571-4. doi: 10.1210/endo.143.5.8861.


The neuroendocrine and immune systems communicate bidirectionally. The neuro-immune-endocrine interface is mediated by cytokines acting as auto/paracrine or endocrine factors regulating pituitary development, cell proliferation, hormone secretion, and feedback control of the hypothalamic-pituitary-adrenal (HPA) axis. At birth or during neonatal ontogenesis, cytokines produce permanent alterations of HPA axis function and the stress response. Overexpressing IL-6 or leukemia inhibitory factor leads to significant changes in pituitary development and functions. Pituitary corticotroph POMC gene expression is regulated by CRH as well as several gp130 cytokines acting as neuro-immuno-endocrine modulators. Conversely, HPA axis functions modulate susceptibility or resistance to inflammatory disease. Cytokines (including IL-1, TNF, and members of the gp130 cytokine family) participate as mediators of a complex HPA axis response to stress and inflammation. Prolonged exposure to proinflammatory cytokines increases levels of the dominant negative glucocorticoid receptor isoform. Nonresponsiveness of the HPA axis to glucocorticoid negative feedback control provides a defense from destructive effects of cytokine excess. At the same time, gp130 cytokines stimulate pituitary suppressor of cytokine signaling (SOCS)-3, which represses cytokine signaling and abrogates cytokine-induced corticotroph POMC gene transcription and ACTH secretion.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, CD / physiology*
  • Cytokine Receptor gp130
  • Cytokines / physiology
  • Endocrine System / physiology*
  • Humans
  • Hypothalamo-Hypophyseal System / growth & development
  • Hypothalamo-Hypophyseal System / physiology*
  • Immune System / physiology*
  • Membrane Glycoproteins / physiology*
  • Nervous System Physiological Phenomena*
  • Neuroimmunomodulation*
  • Pituitary-Adrenal System / growth & development
  • Pituitary-Adrenal System / physiology*


  • Antigens, CD
  • Cytokines
  • IL6ST protein, human
  • Membrane Glycoproteins
  • Cytokine Receptor gp130