INFLUENCE OF CYTOKINES ON THE DENSITY OF BETA(2)-ADRENERGIC RECEPTORSON PERIPHERAL-BLOOD MONONUCLEAR-CELLS IN-VITRO

Previous investigations have demonstrated a decrease of the number of beta(2)-adrenergic receptors (beta 2R) on peripheral blood mononuclear cells (PBMC) in patients with rheumatic diseases that correlated with the systemic inflammatory activity, However, the main factor(s) modul ating the beta 2R on lymphocytes in inflammatory diseases are still un identified, The present study aimed at evaluating the influence of int erleukin 1 beta (IL-1 beta) and interleukin 2 (IL-2) on the number a:n d on the dissociation constant (KD) of beta 2R on PBMC in vitro, PBMC from healthy volunteers were incubated,vith different concentrations o f IL-1 beta (10-100 U/ml) or IL-2 (10-50 U/ml) for 1, 6, 12, 24 and 72 hours (h), respectively, Cultures,vith medium alone served as control s, beta 2R were determined using a radioligand binding assay with (125 )Iodo-cyanopindolol. The results showed a significant spontaneous decl ine of beta 2R after 72 h (mean +/- SEM = 2674 +/- 392 binding sites/c ell (bs/c) vs, 1131 +/- 149 bs/c P < 0.02), IL-2 at a concentration of 50 U/ml diminished this spontaneous reduction of beta 2R numbers sign ificantly (control: 1439 +/- 139 bs/c vs, IL-2: 1724 +/- 107 bs/c, P < 0.05), However, beta 2R densities did not hold baseline levels and we re still significantly lower as compared to preculture values, Incubat ion with 100 U/mlIL-1 beta for 6 h induced a significant increase of b eta 2R densities (control: 1760 +/- 214 bs/c wt. IL-1: 2233 +/- 424 bs /c, P < 0.05), After 72 h stimulation with IL-1 beta there was a signi ficant decrease of beta 2R (1479 +/- 112 bs/c) as compared to control cultures (1958 +/- 239, P < 0.05), No significant changes of the KD's under either culture condition were observed, In conclusion, these dat a demonstrate that IL-1 beta and IL-2 modulate the beta 2R status on P BMC, In this respect the two cytokines seem to elicit contrary effects on the density of beta 2R on PBMC in vitro, The significance of these findings for lymphocyte function remains to be clarified.