Norepinephrine content in primary and secondary lymphoid organs is altered in rats with adjuvant-induced arthritis

Chemical sympathectomy of secondary lymphoid organs with sparing of the hind limbs exacerbates adjuvant-induced arthritis (AA) in Lewis rats supporting a role for noradrenergic (NA) innervation of the immune system in AA pathology. The present study examines sympathetic innervation of lymphoid organs from Lewis rats 32 days after treatment with complete Freund's adjuvant (CFA) or vehicle using fluorescence histochemistry for localization of catecholamines (CA) and high-performance liquid chromatography with electrochemical detection (LCEC) for measurement for norepinephrine. The thymus from AA rats was significantly reduced in size, while secondary lymphoid organs, i.e., spleen and draining lymph nodes (DLN), were significantly enlarged compared with that seen in vehicle-treated controls. Fluorescence histochemistry revealed no apparent differences in the density of NA innervation, or the intensity of staining in sympathetic nerves in any of the secondary lymphoid organs from AA rats compared with that observed in control animals. However, there was an apparent increase in the density of NA nerve fibers in the thymus of AA rats. Norepinephrine (NE) concentration (pmol NE per g or mg wet weight), in the thymus from AA rats was significantly increased. Conversely, a significant decrease in splenic and lymph node NE concentration was measured in adjuvant-treated animals compared with that seen in vehicle-treated rats. Total NE content (pmol NE per whole organ weight) in lymphoid organs was not altered, except in popliteal lymph nodes (PLN), where it was increased. Collectively, our findings suggest that changes in NA innervation of lymphoid organs from AA rats result largely from increases or decreases in organ mass. Since NE released from NA nerves acts in a paracrine fashion, changes in lymphoid tissue volume that result from enhanced proliferation, migration, or cell death can make a significant difference in the availability of NE for interaction with immune target cells in these organs, even in the absence of a change in NE metabolism. Decreased thymic weight and increased spleen and lymph node weight should increase and decrease NE availability for interaction with target cells, respectively. Additionally, in PLN (a site where the highest concentration of antigen is encountered) an increase in total NE content suggests compensatory changes in NE metabolism.