Neuroendocrine and immunological mechanisms in stress-induced immunomodulation.
Here, we report that emotional stressors (restraint, footshock) can affect humoral immune responses as well as the capacity of immune and accessory cells to secrete interleukins. Acute restraint stress (5 min) caused a 4- to 6-fold enhancement of splenic antibody responses to sheep red blood cells. In an attempt to study endocrine mechanisms, we administered antibodies raised in rats to corticotropin releasing factor (CRF). Intravenous administration of these antibodies prior to stress-exposure and immunization prevented the stress-induced increase in the humoral response. In a parallel experiment, we observed that CRF-immunoneutralization prevented the restraint stress-induced increase in plasma ACTH concentrations, but was without effect on plasma prolactin, melanocyte stimulating hormone, adrenaline and noradrenaline responses. These data suggest the presence of an indirect pathway involving ACTH and related peptides by which CRF controls humoral responses to stress. A pathway involving a direct mechanism of CRF at the level of the immune cells will be discussed. In a set of other experiments, we addressed the question of whether interleukin-1 and interleukin-6 plasma levels induced by injection of endotoxin could be modulated by emotional stress. Exposure to prolonged footshock stress (20 min) prior to endotoxin injection resulted in a blunted plasma ACTH and interleukin-1 response, without affecting the endotoxin-induced plasma interleukin-6 response. These data suggest that at least one level at which emotional stress may influence immune function is by changing the capacity of immune cells to produce and/or secrete immune regulatory interleukins.
Berkenbosch
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F
Departement of Pharmacology, Medical Faculty, Free University, Amsterdam, The Netherlands.
Wolvers
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DA
Derijk
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D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000917:Antibody Formation; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009490:Neurosecretory Systems / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000276:immunology*
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone