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

Background. Cytokines mediate the metabolic and physiologic responses to in jury and infection. Anterior pituitary cells express receptors for tumor ne crosis factor (TNF) and interleukin 1 (IL-1), which can signal these cells to release corticotropin, growth hormone, and cytokines such as IL-l and ma crophage migration inhibitory factor. This interaction provides an importan t link between the immune system and the neuroen-docrine system. We reasone d that pituicytes activated with TNF or IL-I might release previously unrec ognized factors that could participate in this signaling from the neuroendo crine to the immune system. Methods. Proteins release from om mt pituicytes (GH(3)) after stimulation w ith proinflammatory cytokines) were, identified by N-terminal amino acid se quencing. Polyclonal antibodies against a peptide corresponding to the N-te rminal amino acid sequence were generated and used to determine the kinetic s of protein release. Results. Cytokine stimulation included the release of a 30-kd protein from rat pituicytes. After the protein was isolated and the N-terminal amino aci d sequence determined a protein database analysis revealed that it is high mobility group-1 (HMG-1) protein. TNF and IL-I induced the release of HMG-1 from pituicytes in a time- and dose-dependent manner. Interferon gamma alo ne din not induce the release of HMG-1, but it enhanced TNF-induced HMG-1 r elease. Conclusion. Stimulation of pituicytes by TNF or IL-I induces the release of HMG-1, which may participate in the regulation of neuroendocrine and immun e responses to infection or injury.