The influence of cyclosporin A on the induction of experimental autoimmune thyroid disease in the PVG/c rat

Abstract

Using an experimental model of autoimmune thyroid disease we have investigated the influence of cyclosporin A (CyA) on the induction of the disease and its potential ability to prevent disease development. PVG/c rats (n = 80) neonatally thymectomized (day 21) and thence sublethally irradiated were divided into eight groups and received either no CyA or oral CyA (10 mg/kg body weight) for varying periods prior to and during disease induction. Serial serum measurements of thyrotropin (TSH) by radioimmunoassay and anti-thyroglobulin autoantibody by enzyme linked immunosorbent assay showed a progressive rise in untreated animals. The rise in serum TSH levels from 349 +/- 15 ng/ml (mean +/- s.e., normal less than 400 ng/ml) at 7 weeks of age to 526 +/- 61 ng/ml at 11 weeks and 820 +/- 54 ng/ml at 15 weeks was not significantly different in animals treated with CyA for periods ranging from 24 h prior to thymectomy to 7 days post-thymectomy. In contrast animals treated for 28 days post-thymectomy showed significantly lower levels of TSH at both 11 weeks (391 +/- 26; P less than 0.02) and 15 weeks (587 +/- 37; P less than 0.005) as compared with untreated animals. Similar though less dramatic changes were seen in intermediate groups. Autoantibody levels in untreated animals rose from initially undetectable levels to 0.451 +/- 0.07 OD (mean +/- s.e.) at 11 weeks and 0.581 +/- 0.041 OD at 15 weeks. Animals treated for at least 4 weeks after thymectomy with CyA had significantly lower levels of antibody at both 11 weeks (0.213 +/- 0.01; P less than 0.001) and 15 weeks (0.337 +/- 0.03; P less than 0.001) of age. Intermediate groups ranged in antibody levels depending on the duration of CyA treatment. Thyroid gland weight (12.7 +/- 2.4 mg/100 g body weight, mean +/- s.e.) and histological grade of thyroiditis (1.8 +/- 0.4, mean +/- s.e.) in the animals treated with CyA for 4 weeks, assessed when the animals were killed at 15 weeks, were smaller and had less severe thyroiditis than untreated thymectomized and irradiated animals (23.8 +/- 2.8 mg/100 g, P less than 0.02 and 2.9 +/- 0.2, P less than 0.05) killed at the same time. CyA given for long enough during induction of experimentally-induced autoimmune thyroid disease delayed the onset of disease and reduced its severity but could not prevent it given over time courses ranging from 48 h prior to thymectomy to 4 weeks after.(ABSTRACT TRUNCATED AT 400 WORDS)