INDUCTION OF INTERFERON-GAMMA INDUCING FACTOR IN THE ADRENAL-CORTEX

Interferon-gamma inducing factor (IGIF) is a recently identified cytok ine also called interleukin-1 gamma (IL-1 gamma) or interleukin-1 gamm a (IL-18), Its biological activity is pleiotropic, and, so far, it has been shown to induce interferon-gamma production in Th1 cells, to aug ment the production of granulocyte-macrophage-CSF, and to decrease tha t of interleukin-10 (IL-10). We first detected newly synthesized IGIF mRNA by differential display in the adrenal gland of reserpine-treated rats and then isolated two transcripts by reverse transcription polym erase chain reaction. They were identified as rat IGIF on the basis of the high homology with mouse: 91% at both the nucleotide and the amin o acid level. Subsequently, we investigated the effects of stress on I GIF mRNA levels and found that acute cold stress strongly induced IGIF gene expression. In. situ hybridization analysis showed that IGIF is synthesized in the adrenal cortex, specifically in the zona reticulari s and fasciculata that produce glucocorticoids. The presence of IGIF m RNA was also detected in the neurohypophysis although induction by str ess was not significant. Our results call for more attention to the ro le of the adrenal gland as a potential effector of immunomodulation an d suggest that IGIF itself might be a secreted neuroimmunomodulator an d play an important role in orchestrating the immune system following a stressful experience.