Catecholamine-induced suppression of interleukin-1 production.
Recent evidence indicates that stress can suppress immune responses and thus increase the severity of viral and neoplastic diseases. Although, the mechanisms for stress-induced modulation of immunologic competence are unclear, neuroendocrine hormones are thought to be involved. A direct suppressive effect could result from the action of neuroendocrine hormones on lymphokine and monokine release. The central role of interleukin-1 (IL-1) in regulating cellular immune responses to infection and neoplasms stimulated the present study evaluating the effects of neuroendocrine hormones on IL-1 production. Norepinephrine and epinephrine inhibited the capacity of gamma interferon and lipopolysaccharide to stimulate IL-1 production from mouse peritoneal macrophages. Moreover, when intracellular and extracellular levels of IL-1 were quantitated, the studies demonstrated a catecholamine-mediated block in IL-1 synthesis without effect on its release. We also observed that exogenous cyclic AMP (cAMP) administered to mouse macrophages suppressed IL-1 production. This, coupled with the capacity of norepinephrine and epinephrine to enhance intracellular cAMP levels in macrophages, strongly suggested that the catecholamine-induced suppression of IL-1 production may be mediated by elevated intracellular cAMP levels. These findings demonstrate that selected stress-related neuroendocrine hormones can modulate IL-1 production by macrophages and further support the hypothesis that alteration of macrophage function by neuropeptides and neurohormones is a significant feature of stress-induced enhancement of viral and neoplastic disease.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D003994:Bucladesine; D007371:Interferon-gamma; D009638:Norepinephrine; D004837:Epinephrine