Previously we demonstrated reduced norepinephrine concentrations in spleens from Lewis rats with adjuvant-induced arthritis (AA), an animal model of rheumatoid arthritis. This study extends these findings, examining the anatomical localization and density of sympathetic nerves in the spleen with disease development. Noradrenergic (NA) innervation in spleens of Lewis rats was examined 28 days following adjuvant treatment to induce arthritis or vehicle for the adjuvant by using fluorescence histochemistry for catecholamines, with morphometric analysis and immunocytochemistry for tyrosine hydroxylase. In AA rats, sympathetic nerve density in the hilar regions, where NA nerves enter the spleen, was increased twofold over that observed in vehicle-treated rats. In contrast, there was a striking twofold decline in the density of NA nerves in splenic regions distal to the hilus in arthritic rats compared with nonarthritic rats. In both treatment groups, NA nerves distributed to central arterioles, white pulp regions, trabeculae, and capsule. However, NA nerve density was reduced in the white pulp but was increased in the red pulp in AA rats compared with non-AA rats. These findings indicate an injury/sprouting response with disease development whereby NA nerves die back in distal regions and undergo a compensatory sprouting response in the hilus. The redistribution of NA nerves from white pulp to red pulp suggests that these nerves signal activated immune cells localized in the red pulp in AA. Although the mechanisms of this redistribution of NA nerves into the red pulp are not known, it may be due to migration from white pulp to red pulp of target immune cells that provide trophic support for these nerves. The redistribution of NA nerves into the red pulp may be critical in modulating immune functions that contribute to the chronic inflammatory stages of arthritis.

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The first step in management of bronchial asthma is to exclude other diseases which may present as wheezing dyspena. Once the diagnosis is confirmed beyond a reasonable doubt, therapy can be initiated. Treatment depends on the type, severity, and duration of the disease. Other factors which dictate the choice of drug are the patient's response, metabolism of the drug, and complications of the disease. Theophylline forms the backbone of asthma therapy. Because of the wide variation in half-life of theophylline in different individuals due to variation in rate of metabolism and elimination, serum levels of theophylline should be monitored whenever possible. Newer antiasthmatic drugs, such as cromolyn sodium and inhaled steroids, are playing an increasing role in treatment of selected patients.