Interferon-γ Modulates Melatonin Production in Rat Pineal Glands in Organ Culture

The effect of interferon-γ (IFN-γ) on melatonin production was determined in rat pineal glands in organ culture. IFN-γ enhanced the production of melatonin in the glands incubated with either 10 nM or 1,000 nM isoproterenol (ISO, a β-adrenergic receptor agonist) but decreased the l00nM ISO response. The enhanced melatonin production was accompanied by either unchanged or a lower level of N-acetyltransferase (NAT) activity, whereas the suppression was accompanied by a reduced NAT activity. IFN-γ did not change the activity of the enzyme hydroxyindole-O-methyltransferase (HIOMT) in the ISO-stimulated pineal glands. The results indicate that IFN-γ has a dual action on the pineal gland: One is to increase melatonin production through yet unknown mechanisms, and the other is to suppress NAT activity. These results also suggest that the pineal gland, under physiological stimulation, is modulated by IFN-γ to increase melatonin production. A hypothetical model is proposed to explain the delicate regulation of pineal function by the immune system.