Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein-1 by pituicytes

Surgery. 1999 Aug;126(2):389-92.


Background: Cytokines mediate the metabolic and physiologic responses to injury and infection. Anterior pituitary cells express receptors for tumor necrosis factor (TNF) and interleukin 1 (IL-1), which can signal these cells to release corticotropin, growth hormone, and cytokines such as IL-1 and macrophage migration inhibitory factor. This interaction provides an important link between the immune system and the neuroendocrine system. We reasoned that pituicytes activated with TNF or IL-1 might release previously unrecognized factors that could participate in this signaling from the neuroendocrine to the immune system.

Methods: Proteins released from rat pituicytes (GH3) after stimulation with proinflammatory cytokines were identified by N-terminal amino acid sequencing. Polyclonal antibodies against a peptide corresponding to the N-terminal amino acid sequence were generated and used to determine the kinetics of protein release.

Results: Cytokine stimulation induced the release of a 30-kd protein from rat pituicytes. After the protein was isolated and the N-terminal amino acid sequence determined, a protein database analysis revealed that it is high mobility group-1 (HMG-1) protein. TNF and IL-1 induced the release of HMG-1 from pituicytes in a time- and dose-dependent manner. Interferon gamma alone did not induce the release of HMG-1, but it enhanced TNF-induced HMG-1 release.

Conclusion: Stimulation of pituicytes by TNF or IL-1 induces the release of HMG-1, which may participate in the regulation of neuroendocrine and immune responses to infection or injury.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line
  • HMGB1 Protein
  • High Mobility Group Proteins / metabolism*
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology*
  • Molecular Sequence Data
  • Pituitary Gland / cytology
  • Pituitary Gland / drug effects*
  • Pituitary Gland / metabolism
  • Rats
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Carrier Proteins
  • HMGB1 Protein
  • High Mobility Group Proteins
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma