Mimicking disruption of brain-immune system-joint communication results in collagen type II-induced arthritis in non-susceptible PVG rats.
The brain-immune system-joint communication is disrupted during collagen type II (CII) arthritis in DA rats. Since PVG rats are not susceptible to arthritis induction, comparison of hypothalamic and peripheral neuro-endocrine and immune responses between immunized DA and PVG rats might help to explain their different susceptibility to develop the disease. PVG and DA rats were immunized with CII. Corticosterone, neurotransmitters, anti-CII antibodies, and cytokine concentrations in plasma, and hypothalamic neurotransmitters and cytokines were determined by ELISA, Luminex, HPLC and RT-qPCR. Adrenalectomy or sham-operation was performed in PVG and DA rats 14 days before immunization. Basal plasma corticosterone and adrenaline concentrations were significantly higher, and plasma cytokines and hypothalamic noradrenaline were lower in PVG rats than in DA rats. While DA rats developed severe arthritis upon immunization (maximum score 16), only 12 out of 28 PVG rats showed minimal symptoms (score 1-2). The density of sympathetic nerve fibers in arthritic joints of DA rats markedly decreased, but it remained stable in immunized PVG rats. The ratio corticosterone to IL-1β levels in plasma was markedly higher in immunized PVG rats than in arthritic DA rats. Adrenalectomy resulted in severe arthritis in PVG rats upon immunization with CII. While DA rats show an altered immune-brain communication that favors the development of arthritis, PVG rats express a protective neuro-endocrine milieu, particularly linked to the basal tone of the HPA axis. Mimicking disruption of this axis elicits arthritis in non-susceptible PVG rats.
Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital Regensburg, Germany.
Christine
C
Wolff
Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital Regensburg, Germany. Electronic address: rainer.straub@ukr.de.
Rainer H
RH
Straub
Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital Regensburg, Germany.
Anja
A
Hahnel
Department of Immunophysiology, Institute of Physiology and Pathophysiology, University of Marburg, Germany.
Anke
A
Randolf
Department of Immunophysiology, Institute of Physiology and Pathophysiology, University of Marburg, Germany.
Johannes
J
Wildmann
Department of Immunophysiology, Institute of Physiology and Pathophysiology, University of Marburg, Germany.
Hugo O
HO
Besedovsky
Department of Immunophysiology, Institute of Physiology and Pathophysiology, University of Marburg, Germany.
Adriana
A
del Rey
D000320:Adrenergic Fibers / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D003345:Corticosterone / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007114:Immunization; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats
D024043:Collagen Type II; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine
Adrenalectomy; Arthritis; HPA axis; Hypothalamus; Sympathetic nervous system