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 th e hind limbs exacerbates adjuvant-induced arthritis (AA) in Lewis rats supporting a role for noradrenergic (NA) innervation of the immune sy stem in AA pathology. The present study examines sympathetic innervati on of lymphoid organs from Lewis rats 32 days after treatment with com plete Freund's adjuvant (CFA) or vehicle using fluorescence histochemi stry for localization of catecholamines (CA) and high-performance liqu id chromatography with electrochemical detection (LCEC) for measuremen t for norepinephrine. The thymus from AA rats was significantly reduce d in size, while secondary lymphoid organs, i.e. spleen and draining l ymph nodes (DLN), were significantly enlarged compared with that seen in vehicle-treated controls. Fluorescence histochemistry revealed no a pparent differences in the density of NA innervation, or the intensity of staining in sympathetic nerves in any of the secondary lymphoid or gans from AA rats compared with that observed in control animals. Howe ver, there was an apparent increase in the density of NA nerve fibers in the thymus of AA rats. Norepinephrine (NE) concentration (pmol NE p er g or mg wet weight), in the thymus from AA rats was significantly i ncreased. Conversely, a significant decrease in splenic and lymph node NE concentration was measured in adjuvant-treated animals compared wi th that seen in vehicle-treated rats. Total NE content (pmol NE per wh ole organ weight) in lymphoid organs was not altered, except in poplit eal lymph nodes (PLN), where it was increased. Collectively, our findi ngs suggest that changes in NA innervation of lymphoid organs from AA rats result largely from increases or decreases in organ mass. Since N E released from NA nerves acts in a paracrine fashion, changes in lymp hoid tissue volume that result from enhanced proliferation, migration, or cell death can make a significant difference in the availability o f 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 N E availability for interaction with target cells, respectively. Additi onally, in PLN (a site where the highest concentration of antigen is e ncountered) an increase in total NE content suggests compensatory chan ges in NE metabolism. (C) 1997 Elsevier Science Ireland Ltd.