Cyclosporine effect on ornithine decarboxylase activity in rat submaxillary lymph nodes. Modulation by parasympathetic nerves

Abstract

This study was performed: (1) to assess whether cyclosporine affected the increase in submaxillary lymph node ornithine decarboxylase activity induced by complete Freund's adjuvant injection to rats bearing a regional parasympathetic decentralization; (2) to examine the effect of cyclosporine on cholinergic markers in submaxillary lymph nodes of rats injected with complete Freund's adjuvant or its vehicle. The unilateral parasympathetic decentralization of the submaxillary lymph nodes was achieved by unilateral chorda tympani section; each rat was also contralaterally sham-operated. A 73% decrease of choline acetyltransferase activity and a 78% decrease of neuronal [ 3H]choline uptake, were found in the ipsilateral side 2 weeks after surgery. Cyclosporine (5 or 20 mg/kg) or its vehicle was s.c. injected once daily for 5 days. Freund's complete adjuvant or its vehicle was injected s.c. 1 h before the 3rd injection of cyclosporine. The animals were killed 2 h after the last cyclosporine injection. Parasympathetic decentralization of the submaxillary lymph nodes was followed, 2 weeks later, by a significant inhibition of cyclosporine activity on Freund's adjuvant-induced ornithine decarboxylase. In rats injected with complete Freund's adjuvant or its vehicle, sympathetic denervation of submaxillary lymph nodes achieved by unilateral superior cervical ganglionectomy, augmented the stimulatory activity of cyclosporine on choline acetyltransferase and neuronal choline uptake. Cyclosporine treatment did not modify the total [ 3H]choline uptake, regardless of Freund's adjuvant injection or of intactness of the sympathetic innervation. Choline acetyltransferase and choline uptake were significantly augmented by the injection of Freund's adjuvant alone. The results indicate that an appropriate parasympathetic local environment is needed for cyclosporine immunomodulation in lymphoid tissue, and that cyclosporine augmented cholinergic activity in submaxillary lymph nodes, an effect amplified by regional sympathetic denervation. Cholinergic markers in lymphoid tissue increased during the immune reaction.