Abstract
Diurnal changes in cyclosporine efficacy to affect ornithine decarboxylase activity, [ 3H]norepinephrine uptake and [ 3H]choline conversion into [ 3H]acetylcholine were examined in rat submaxillary lymph nodes. Cyclosporine (5 or 20 mg/kg) caused a dose-dependent decrease in lymph node ornithine decarboxylase, being active at 5 or 20 mg/kg in Freund's adjuvant-treated rats, and at 20 mg/kg in rats treated with the adjuvant's vehicle. In immunized rats the lower cyclosporine dose was ineffective when injected during the night. Cyclosporine increased lymph node [ 3H]norepinephrine uptake dose dependently, with significant differences between the 20 mg/kg dose and controls in vehicle-treated rats and between 5 or 20 mg/kg and controls in Freund's adjuvant-treated rats. In immunized rats, 5 mg/kg cyclosporine increased [ 3H]norepinephrine uptake when injected at 13:00 or 17:00 h. Both doses of cyclosporine augmented lymph node synthesis of [ 3H]acetylcholine to a similar extent. In immunized and non-immunized rats cyclosporine suppressed the diurnal rhythm of lymph node adrenergic and cholinergic activity found in controls. After unilateral sympathetic denervation (by superior cervical ganglionectomy) and/or unilateral parasympathetic decentralization (by chorda tympani section), cyclosporine (5 mg/kg) decreased Freund's adjuvant-induced activation of lymph node ornithine decarboxylase when injected at 17:00 or 01:00 h. On the sham-operated side, cyclosporine was effective when injected at 17:00 h only. Decentralization, or a combined ganglionectomy plus decentralization, decreased lymph node ornithine decarboxylase activity. The results indicate active regulation of the effects of cyclosporine in submaxillary lymph nodes by local autonomic nerves.
Published Version
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