Effects of a chronic inflammatory stress on levels of pro-opiomelanocortin-derived peptides in the rat spleen and thymus

Abstract Adjuvant-induced arthritis (AA) in specific strains of rats is an immunologically mediated inflammatory disease which is also characterised by activation of the endocrine system. To further investigate the effects of AA on processing of the pro-opiomelanocortin (POMC) precursor in rat immune tissues, we utilised radioimmunoassays for adrenocorticotropin (ACTH), β-endorphin and α-melanocyte-stimulating hormone (α-MSH) to measure these peptides in the spleen and thymus. 14 days following adjuvant injection, spleen levels of ACTH were elevated in the AA group (4.47 ± 1.04 ng/g tissue, n = 9) compared to controls 2.42±0.4 ng/g) and exacerbation of the disease by removal of circulating glucocorticoids through bilateral adrenalectomy (ADX) resulted in further elevation of spleen ACTH (5.11 ± 1.22 ng/g). β-Endorphin levels in both the AA (10.60 ± 1.61 ng/g) and AA/ADX (13.37 ± 2.36 ng/g) groups were higher than controls 5.57 ± 0.65 ng/g). Conversely, α-MSH spleen levels were decreased in the AA (2.89 ± 0.22 ng/g) and AA/ADX (2.22 ± 0.33 ng/g) groups compared to controls (4.62 ± 0.45 ng/g) and were also decreased following adrenalectomy. In the thymus, ACTH levels were elevated in the AA group (8.95 ± 1.41 ng/g) compared to controls (5.79 ± 0.63 ng/g), and the same pattern wasevident for thymic α-MSH (0.64 ± 0.08 ng/g in AA animals compared to control levels of 0.35 ± 0.03 ng/g). Following G50 gel filtration, ACTH and β-endorphin immunoreactivities (ir) were present in both spleen and thymus as two peaks, one which eluted near the void volume and one which eluted in a lower molecular mass position than the standards. However, ir-ACTH and ir-β-endorphin were present in multiple peaks in AA spleen extracts, indicating extensive processing. These data are the first evidence that ir-ACTH and ir-β-endorphin tissue content and POMC processing in the spleen and thymus can be influenced by a chronic stress.