Chronic terbutaline treatment desensitizes β-adrenergic inhibition of lymphocyte activation in healthy volunteers

1 A substantial body of evidence has accumulated that β-adrenoceptor mediated increases in human lymphocyte cyclic AMP can inhibit activation of resting lymphocytes. The aim of this study was to determine whether this effect might desensitize during chronic β-adrenoceptor agonist treatment. We assessed the effects of 2 weeks treatment with the β₂-adrenoceptor agonist terbutaline (3 × 5 mg day⁻¹ p.o.) on isoprenaline-induced inhibition of concanavalin A-evoked lymphocyte activation in nine healthy male volunteers. Lymphocyte activation was determined by [³H]-thymidine incorporation (as a measure of proliferation), and inositol phosphate formation was assessed in [³H]-myo-inositol prelabelled lymphocytes in the presence of 10 mm LiCl.

2 Terbutaline treatment caused a significant reduction in isoprenaline (1 nm– 10 μm)-induced increases in lymphocyte cyclic AMP content; the maximal increase was 14 ± 3 pmol/10⁶ cells before and 7 ± 2 pmol/10⁶ cells (n= 9, P < 0.05) after terbutaline treatment.

3 The mitogen concanavalin A (Con A, 1–32 μg ml⁻¹)-induced increase in inositol phosphate formation was significantly enhanced after terbutaline treatment (max. increase before treatment: 255 ± 25% above basal; after treatment 453 ± 16% above basal; n= 9, P < 0.001), while isoprenaline (1 nm– 10 μm)-induced inhibition of Con A (16 μg ml⁻¹)-evoked increases in inositol phosphate formation was significantly reduced after the terbutaline treatment (max. inhibition before treatment: 22 ± 4%; after treatment 9 ± 1%, n= 9, P < 0.01).

4 Con A (1.25 – 10 μg ml⁻¹)-induced increases in [³H]-thymidine incorporation into the lymphocytes (as a measure of proliferation) was not affected by the terbutaline treatment. On the other hand, isoprenaline (1 nm– 1 μm)-induced inhibition of Con A (5 μg ml⁻¹)-evoked lymphocyte proliferation (max. inhibition: 33 ± 7%, n= 9) was almost completely abolished after the terbutaline treatment.

5 We conclude that chronic treatment with terbutaline desensitizes lymphocyte β₂-adrenoceptors and, therefore, the inhibitory effect of cyclic AMP on lymphocyte activation.