Interaction between the adrenal and the pineal gland in chronic experimental inflammation induced by BCG in mice

Objective: To investigate the adrenal gland influence on diurnal rhythm of chronic inflammation induced by BCG in mice and its interaction with the pi neal gland. Methods: C57B1/6 mice were injected with BCG in the footpad and maintained in a 12/12 h light-dark cycle. Air the experimental manipulations were done after 20-45 days. Paw swelling was measured every 4 h for 48 or 72 h and d ecomposed by Fourier transformation. Vascular permeability was evaluated by Evans Blue overflow, in mice killed at midday or midnight. 6-Sulphatoxymel atonin urine concentration was determined by radioimmunoassay in samples ta ken during the dark or light phase. Results: Adrenalectomy or metyrapone treatment abolished the paw swelling d iurnal. rhythm, the nocturnal reduction in vascular permeability, and the n octurnal increase in 6-sulphatoximelatonin in the urine. Nocturnal administ ration of melatonin to adrenalectomized mice restored the paw swelling diur nal variation and the reduction of vascular permeability of the inflamed pa w. Conclusion: Adrenal cortical hormones are important for the maintenance of the diurnal rhythm of chronic inflammation (paw swelling and vascular perme ability), probably by promoting a nocturnal surge of melatonin, which is th e hormone that modulates the diurnal variation of chronic inflammation.