Effect of β2-adrenergic receptor agonists on intercellular adhesion molecule (ICAM)-1, B7, and CD40 expression in mixed lymphocyte reaction

Background. The plasma interleukin (IL)-18 level is elevated in acute rejection after organ transplantation. Although β2-adrenergic receptor (AR) agonists suppress the rejection of organ and tissue transplants, little is known about their action mechanisms. We examined the effects of endogenous catecholamines and β2-AR agonists on the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) in human mixed lymphocyte reaction (MLR) and in an in vitro model of acute rejection in the presence or absence of IL-18. Methods. ICAM-1, B7.1 B7.2, CD40, and CD40L expression on monocytes was measured by flow cytometry, and the production of interferon (IFN)-γ and IL-12 was determined by enzyme-linked immunosorbent assay. Lymphocytes proliferation in MLR was measured by [ ³H]-thymidine uptake. The relevant AR subtypes were characterized using subtype-selective agonists and antagonists. Results. β2-AR agonists inhibited the expression of ICAM-1 and CD40 during MLR in the absence of IL-18. Among IL-18-induced expression of ICAM-1, B7.1, B7.2, CD40, and CD40L, β2-AR agonists inhibited ICAM-1 and CD40 expression. β2-AR agonists prevented the production of IFN-γ and IL-12 in the presence of IL-18 but had no effect in the absence of IL-18. β2-AR agonists inhibited lymphocyte proliferation in IL-18-treated MLR. Conclusions. We found that β2-AR agonists strongly inhibited the expression of ICAM-1 and CD40, irrespective of the presence or absence of IL-18, which is different from that of histamine and prostaglandin E2.