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Endogenous α‐MSH modulates the Hypothalamic‐Pituitary‐Adrenal Response to the Cytokine Interleukin‐1β
Author(s) -
Anastasios D. Papadopoulos,
Sharon L. Wardlaw
Publication year - 1999
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.1999.00327.x
Subject(s) - medicine , endocrinology , corticosterone , endogeny , adrenocorticotropic hormone , antiserum , cytokine , hormone , peptide hormone , melanocyte stimulating hormone , chemistry , antibody , immunology
We and others have previously shown that exogenous α ‐MSH antagonizes the stimulatory effects of the cytokine interleukin (IL)‐1 on the hypothalamic‐pituitary‐adrenal (HPA) axis. It is currently unknown, however, if endogenous α ‐MSH plays a physiological role in regulating the HPA response to IL‐1. We have therefore examined the HPA response to IL‐1 β in rats pretreated with an affinity purified α ‐MSH antiserum (AS) infused intracerebroventricularly to neutralize endogenous α ‐MSH within the brain. α ‐MSH AS or a similarly purified fraction of normal rabbit serum (NRS) was injected intracerebroventricularly at 16 h and at 1 h prior to the i.c.v. injection of IL‐1 β (2 ng or 20 ng) and blood samples were collected through an indwelling atrial catheter. After 2 ng IL‐1 β , the adrenocorticotropic hormone (ACTH) response was significantly greater in the α ‐MSH AS treated rats (n=7) compared to the NRS treated rats (n=7) (P<0.01); the mean ACTH level rose to a peak of 594±208 pg/ml in the α ‐MSH AS treated rats vs 274±122 pg/ml in the NRS treated rats. The area under the ACTH response curve in the α ‐MSH AS treated animals was 181% of that in the NRS treated animals (P<0.05). A significant effect of α ‐MSH AS on the corticosterone response to i.c.v. IL‐1 β was also noted during the first 3 h of the study (P<0.05). The mean area under the corticosterone response curve for the first 3 h in the α ‐MSH AS treated animals was 144% of that in the NRS treated animals (P<0.05). After 20 ng IL‐1 β , the ACTH response over time was again significantly greater in the α ‐MSH AS treated rats (n=8) compared to the NRS treated rats (n=9) (P<0.02); the mean ACTH level rose to a peak of 673±190 pg/ml after α ‐MSH AS vs 490±115 pg/ml after NRS. Corticosterone levels rose to a peak of 42±3.9 μg/dl in the α ‐MSH AS treated rats vs 37±4.6 μg/dl in the NRS treated rats; this difference was not significant. We conclude that the IL‐1 β induced stimulation of ACTH is significantly enhanced by antagonizing the activity of α ‐MSH. These results support a physiological role for endogenous α ‐MSH in limiting the HPA response to this inflammatory cytokine.