Interleukin-1, but Not Stress, Stimulates Glucocorticoid Output during Early Postnatal Life in Micea


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    This work was supported by the Volkswagen Stiftung and the Swiss National Research Council.

Address for correspondence: Dr. Hugo O. Besedovsky, Division of Immunophysiology, Institute of Physiology, Medical Faculty, Philipps-University, D-35037 Marburg, Germany.


Abstract: The development of neuroendocrine functions depends not only on genetically determined mechanisms but also on phenotypic signals. Some of these signals may derive from the immune system. For example, interleukin-1β (IL-1β) stimulates glucocorticoid output during the early postnatal period, and administration of this cytokine at birth induces permanent alterations in the HPA axis in adulthood. We have extended these studies and found that the glucocorticoid response elicited in 5-day-old mice by a low dose of IL-1β is not desensitized by previous exposure to the cytokine. We have also compared the magnitude of the increase in corticosterone levels induced by IL-1 in 3-day-old and adult mice to that caused by acute stress. IL-1β and acute stress caused a comparable increase in corticosterone levels in adult mice. In newborn mice, however, IL-1β, but not restraint or cold stress, stimulated corticosterone output. Thus, IL-1β can elicit a corticosterone response during the postnatal stress-hyporesponsive period. Furthermore, when the corticosterone levels attained following IL-1β administration were compared to the basal levels of the hormone at a given age, the increase in plamsa corticosterone levels was several fold higher in newborn than in adult animals. These data, together with the long-lasting endocrine effects of cytokine exposure at birth, suggest an important role of immune cytokines in the programming of neuroendocrine functions during ontogeny.