Endotoxin-induced reduction of β-adrenergic binding sites on splenic lymphocytes [formula omitted] and [formula omitted]: Its modulation by anterior hypothalamic lesions

Abstract

Bacterial endotoxin induced a 38% decrease in the number of β-adrenergic binding sites (Bmax) on splenic lymphocytes, four days after intraperitoneal administration to guinea pigs. No change in the affinity (Kd) for [125-I]-cyanopindolol ([125-I]-CYP) binding was observed. Incubation of guinea pig splenocytes in vitro with different concentrations of bacterial endotoxin for 24 hours resulted in an increased incorporation of [ 3H]-thymidine, a parameter for lymphocyte activation. Activation of splenic lymphocytes with the optimal endotoxin concentration of 100 μg/ml for 24 hours induced a 27% decrease in the Bmax whereas the Kd for [125-I]-CYP binding was not changed. Based on these findings, we speculate that activation of lymphocytes with endotoxin in vitro and in vivo is associated with a reduction in the number of β-adrenergic binding sites on these cells. Anterior hypothalamic (AHA) lesions protected against the endotoxin-induced reduction in the number of β-adrenergic binding sites on lymphocytes. The protective effect of these lesions could not be related to alterations in the plasma levels of cortisol, triiodothyronine (T3), thyroxine (T4), adrenaline and noradrenaline or to splenic noradrenaline content. Since AHA lesions have been shown to inhibit several lymphocyte functions, it is suggested that these lesions prevent lymphocyte activation after in vivo endotoxin administration and through this abrogate the reduction of the β-adrenergic binding sites.