BETA(2)-AGONISTS PREVENT TH1 DEVELOPMENT BY SELECTIVE-INHIBITION OF INTERLEUKIN-12

Interleukin 12 (IL-12) plays a central role in the immune system by sk ewing the immune response towards T helper 1. (Th1) type responses whi ch;are characterized by high interferon-gamma and low IL-4 production. In this report we present evidence that beta(2)-agonists inhibit IL-1 2 production by both human monocytes in response to lipopolysaccharide (LPS) and dendritic cells stimulated via CD40. Inhibition of IL-12 pr oduction is selective, as other cytokines produced by monocytes are un affected. IL-12 inhibition is dependent on beta(2)-adrenoceptor stimul ation and correlates with increased levels of intracellular cAMP. In c onjunction with their ability to suppress IL-12 production, when beta( 2)-agonists are added at priming of neonatal T lymphocytes, they inhib it the development of Th1-type cells, while promoting T helper 2 (Th2) cell differentiation. Further, the in vivo administration of a therap eutic dose of salbutamol results in the selective inhibition of IL-12 production by whole blood lymphocytes stimulated in vitro with LPS. Th ese findings provide new insight into the immunological consequences o f the clinical use of beta(2)-agonists and may suggest new approaches for the treatment of Th1-mediated diseases.