DIURNAL CHANGES IN CYCLOSPORINE EFFECT ON ORNITHINE DECARBOXYLASE ANDNORADRENERGIC AND CHOLINERGIC ACTIVITIES IN SUBMAXILLARY LYMPH-NODES

Diurnal changes in cyclosporine efficacy to affect ornithine decarboxy lase activity, [H-3]norepinephrine uptake and [H-3]choline conversion into [H-3]acetylcholine were examined in rat submaxillary lymph nodes. Cyclosporine (5 or 20 mg/kg) caused a dose-dependent decrease in lymp h node ornithine decarboxylase, being active at 5 or 20 mg/kg in Freun d's adjuvant-treated rats, and at 20 mg/kg in rats treated with the ad juvant's vehicle. In immunized rats the lower cyclosporine dose was in effective when injected during the night. Cyclosporine increased lymph node [H-3]norepinephrine uptake dose dependently, with significant di fferences between the 20 mg/kg dose and controls in vehicle-treated ra ts and between 5 or 20 mg/kg and controls in Freund's adjuvant-treated rats. In immunized rats, 5 mg/kg cyclosporine increased [H-3]norepine phrine uptake when injected at 13:00 or 17:00 h. Both doses of cyclosp orine augmented lymph node synthesis of [H-3]acetylcholine to a simila r extent. In immunized and non-immunized rats cyclosporine suppressed the diurnal rhythm of lymph node adrenergic and cholinergic activity f ound in controls. After unilateral sympathetic denervation (by superio r cervical ganglionectomy) and/or unilateral parasympathetic decentral ization (by chorda tympani section), cyclosporine (5 mg/kg) decreased Freund's adjuvant-induced activation of lymph node ornithine decarboxy lase when injected at 17:00 or 01:00 h. On the sham-operated side, cyc losporine was effective when injected at 17:00 h only. Decentralizatio n, or a combined ganglionectomy plus decentralization, decreased lymph node ornithine decarboxylase activity. The results indicate active re gulation of the effects of cyclosporine in submaxillary lymph nodes by local autonomic nerves.