Norepinephrine-dependent activation of the neuroimmune system is counter-regulated by IL-1RA (B59)

Abstract Stress negatively impacts well-being and is linked to a variety of diseases including heart disease and cancer. It is known that stress modulates the immune defense system, but the mechanisms involved are not well established. Here we report that norepinephrine (NE) is a rapid activator of the neuroimmune system as measured by a loss of interest in the social environment. C57BL/6J mice were injected with 1.5 mg/kg of NE (I.P.) and social exploration (SE) was measured over a 24-hour period. Peak decrease in SE was observed 30 min after NE injection (74.1 ± 4.7 % reduction in SE) and full recovery was observed 8 hours following NE treatment. This decrease appears linked to a brain-based up-regulation of IL-1 alpha (370 %) and TNF alpha mRNA (260 %). Additionally, Kineret®, a derivatized recombinant IL-1RA used in the treatment of rheumatoid arthritis, hastened recovery from NE-induced neuroimmune system activation by 31.1%. These results show that NE actives the neuroimmune system, which IL-1RA treatment can ameliorate.