Publications

Interleukin 2 (IL-2) receptors are expressed on activated T cells and in select T-cell leukemias. Recently, it has been demonstrated that at least two classes of receptor for IL-2 exist with markedly different affinities for ligand. All known biological actions of IL-2 have been correlated with occupancy of high-affinity sites; the function of the low-affinity sites remains unknown. Receptor-mediated endocytosis is the primary means of internalization of cell-surface receptors and their ligands. The internalization of IL-2 bound to high- and low-affinity receptor sites was studied in a human T-cell lymphotrophic virus type 1 (HTLV-1)-infected human T-cell leukemia cell line and in a cloned murine cytotoxic T-cell line (CTLL). Internalization of IL-2 occurred only when bound to high-affinity sites. In addition, an anti-receptor antibody (anti-Tac), which binds equally well to high- and low-affinity sites, demonstrated no detectable internalization. The implications of these findings as they relate to IL-2 receptor structure and function are discussed.

In a double-blind, randomized, crossover study in ten patients with asthma, the effects on specific airway resistance of esmolol, a new ultra-short-acting beta 1-selective adrenoceptor blocker, were compared with those of placebo. Specific airway resistance was measured during increasing doses of esmolol infusion, during dry air provocation tests, and following isoproterenol inhalation. These same studies were later carried out on six of ten patients following intravenous propranolol infusion. All patients were able to tolerate the maximum dose of esmolol (300 micrograms/kg/min); treatment differences between esmolol and placebo were not found. In contrast, intravenous propranolol produced marked symptomatic bronchoconstriction after the lowest dose (1 mg) in two of six patients. Esmolol produced slight but statistically significant enhancement of patients' sensitivity to dry air provocation. Similarly, a slight but significant inhibition of bronchomotor sensitivity to isoproterenol was noted during esmolol infusion. After infusion of 5 mg of intravenous propranolol, one of four patients had a clinically significant increase in sensitivity to dry air. It is concluded that esmolol, because of its short duration of action and relative lack of effect on airway resistance, may be preferred over propranolol in patients with asthma who require treatment with an intravenous beta-blocking agent.