OBJECTIVE: To explore the hypothesis that, in parallel with alterations in the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system, hypothalamic cytokine expression and monoaminergic neurotransmitter concentrations are affected during the course of arthritis development induced by type II collagen. This hypothesis was based on evidence that acute inflammatory processes induce cytokine expression in the brain and affect neuronal activity. We also studied whether depletion of hypothalamic noradrenaline can affect peripheral joint disease. METHODS: Hypothalamic cytokine gene expression and neurotransmitter concentration, parameters of inflammation, and joint innervation were evaluated during arthritis development in rats induced by injection of type II collagen in Freund's incomplete adjuvant. Noradrenergic neurons in the brain were depleted with 6-hydroxydopamine. RESULTS: Transiently increased corticosterone levels, followed by increased adrenaline levels and hypothalamic interleukin-1beta (IL-1beta) and IL-6 overexpression were observed only during the induction phase of the disease. Hypothalamic noradrenaline content was increased during the symptomatic phase and was paralleled by a gradual loss of noradrenergic fibers in the joints. The positive correlation between hypothalamic IL-1beta expression and noradrenaline content in control groups was not observed in rats in which arthritis developed. Depletion of hypothalamic noradrenergic neurons when arthritis was established did not affect the course of the disease. CONCLUSION: The dissociation between hypothalamic cytokine gene expression and noradrenergic neuronal activity, the lack of sustained stimulation of the stress axes, and the loss of sympathetic signals in the joints indicate a disruption in communication between afferent immune messages to the central nervous system and 2 main efferent antiinflammatory pathways under control of the brain during collagen-induced arthritis.
OBJECTIVE: To explore the hypothesis that, in parallel with alterations in the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system, hypothalamic cytokine expression and monoaminergic neurotransmitter concentrations are affected during the course of arthritis development induced by type II collagen. This hypothesis was based on evidence that acute inflammatory processes induce cytokine expression in the brain and affect neuronal activity. We also studied whether depletion of hypothalamic noradrenaline can affect peripheral joint disease. METHODS: Hypothalamic cytokine gene expression and neurotransmitter concentration, parameters of inflammation, and joint innervation were evaluated during arthritis development in rats induced by injection of type II collagen in Freund's incomplete adjuvant. Noradrenergic neurons in the brain were depleted with 6-hydroxydopamine. RESULTS: Transiently increased corticosterone levels, followed by increased adrenaline levels and hypothalamic interleukin-1beta (IL-1beta) and IL-6 overexpression were observed only during the induction phase of the disease. Hypothalamic noradrenaline content was increased during the symptomatic phase and was paralleled by a gradual loss of noradrenergic fibers in the joints. The positive correlation between hypothalamic IL-1beta expression and noradrenaline content in control groups was not observed in rats in which arthritis developed. Depletion of hypothalamic noradrenergic neurons when arthritis was established did not affect the course of the disease. CONCLUSION: The dissociation between hypothalamic cytokine gene expression and noradrenergic neuronal activity, the lack of sustained stimulation of the stress axes, and the loss of sympathetic signals in the joints indicate a disruption in communication between afferent immune messages to the central nervous system and 2 main efferent antiinflammatory pathways under control of the brain during collagen-induced arthritis.
Authors: Jon Lampa; Marie Westman; Diana Kadetoff; Anna Nordenstedt Agréus; Erwan Le Maître; Caroline Gillis-Haegerstrand; Magnus Andersson; Mohsen Khademi; Maripat Corr; Christina A Christianson; Ada Delaney; Tony L Yaksh; Eva Kosek; Camilla I Svensson Journal: Proc Natl Acad Sci U S A Date: 2012-07-16 Impact factor: 11.205
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