CATECHOLAMINES AND LIPOPOLYSACCHARIDE SYNERGISTICALLY INDUCE THE RELEASE OF INTERLEUKIN-6 FROM THYMIC EPITHELIAL-CELLS

The thymus as the major site of T-cell development is exposed to circu lating hormones as well as to neurotransmitters released from peripher al nerves. We investigated the influence of catecholamines on the synt hesis of interleukin-1 (IL-1) and IL-6 by cultured rat thymic epitheli al cells. Basal or lipopolysaccharide (LPS)-stimulated production of I L-1 was not affected by catecholamines. Release of IL-6 was stimulated only scarcely by catecholamines or tumor necrosis factor-alpha (TNF-a lpha) and moderately by LPS alone. However, co-stimulation with adrena line, noradrenaline, or the beta-adrenoceptor agonist isoproterenol (i soprenaline) had all additive (TNF-alpha) or synergistic (LPS) effect on IL-6 release. The synergistic effect was dose-dependent on catechol amine or LPS concentrations. It was mediated by beta-adrenoceptors tha t are linked to elevation of intracellular cAMP levels, since it was p romoted by beta-adrenoceptor agonists and could be blocked by beta-adr enoceptor antagonists. Go-incubation of LPS with agents directly raisi ng cAMP-levels like forskolin or dibutyryl cAMP yielded even stronger IL-6 induction. After co-stimulation IL-6 mRNA was first detected afte r 3-4 h and a constant increase of IL-6 bioactivity in the culture sup ernatant was measured for up to 48 h. Since IL-6 is an important facto r for thymocyte differentiation and proliferation, the findings demons trate an influence of neuronal or hormonal catecholamines on the thymi c microenvironment that is created by thymic epithelial cells. (C) 199 8 Elsevier Science B.V. All rights reserved.