Bedeutung des Zusammenspiels von Zytokinen und Monaminen auf diversen ZNS-Niveaus für Verlauf und Suszeptibilität einer Arthritis

• Antragstellerinnen / Antragsteller: Professorin Adriana del Rey, Ph.D.; Professor Dr. Rainer H. Straub
• Fachliche Zuordnung: Rheumatologie
• Förderung: Förderung von 2005 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5447080

Asevere disruption oft he brain -immune system - joint communication in arthritic rats was found as attested by a) inadequate low endogenous corticosterone production in relation to inflammation and although hypothalamic noradrenalin concentration was increased, b) sympathetic activity was elevated but nerve fibers were lost in synovial tissue, c) hypothalamic expression of the pro-inflammatory cytokines IL-1ß and IL-6 was unexpectedly decreased when the disease is manifested (an increase was expected due to penpheral inflammatory and painful stimuli), and d) depletion of brain noradrenergic neurons at this time did not influence arthritis. Thus, collagen type II (CM) arthritis in rats mimics many aspects of rheumatoid arthritis, but the reasons for the disruption of the brain - immune system - joint communication are unknown. Now, we will extent our earlier work by a) evaluating the relevance of the disruption of the brain-immune system-joint communication, and the effects of 1L-Iß and IL-6 neutralization and administration of IL-10 and of an adenoviral vector that blocks NF-KB effects in the bram for the susceptibility to the disease, b) studying the influence of IL-1ß and IL-6 on catecholamine/serotonin release from hypothalamic tissue slices obtained from arthritic rats, and c) investigating histologically distinct anatomical monoaminergic structures of the central nervous system that we have found to be functionally affected during expenmental arthritis. The experiments in this project will focus on possible molecular factors, anatomical neuronal pathways, and experimental therapies that target disruption of brain-immune system-joint communication in experimental arthritis.

• DFG-Verfahren: Sachbeihilfen