It is well known that IL-12 plays a central role in the initiation and control of allogeneic immune response. It promotes the proliferation of lymphocytes and NK cells, cytotoxic activity of NK cells, and CTL. It was recently shown that IL-12 is involved in the regulation of T helper Th1-Th2 responses by exerting stimulatory effects on Th1 and inhibitory effects on Th2. This regulatory role is believed to result from the ability of IL-12 to induce IFN-γ production in activated T cells and NK cells.[1 and 2] Th1 cytokines (IL-2 and IFN-γ) promote both CTL and delayed-type hypersensitivity (DTH) responses, which are considered the principal effector mechanisms of allograft rejection. Diltiazem, a calcium channel blocker used in organ transplantation, is often included in clinical protocols in association with cyclosporin A and corticosteroids.[3] It was used initially because of its antinephrotoxic and antihypertensive effects, so that the undesirable side effects induced by immunosuppressive therapy could be reduced. We previously studied the effect of diltiazem on human mixed lymphocyte reactions (MLR) and on isolated human monocytes, showing the capacity of this drug to affect proinflammatory cytokine production.[4 and 5] Since dendritic cells (DCs) are the most effective antigen-presenting cells (APCs) to prime naive T cells, we were interested in determining the influence of diltiazem on human DCs. Human DCs generated from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) have been characterised as immature DCs. To become fully potent APCs, DCs must undergo maturation induced either by a proinflammatory signal such as lipopolysaccharide (LPS) or by interaction with CD40L expressed on activated T lymphocytes. [6] The ability of mature DCs to act as potent APCs is due to their high expression of MHC and costimulatory molecules and also to their production of cytokines, especially IL-12. Therefore, we determined the effect of diltiazem on cytokine production by human DCs with a particular interest in IL-1β, IL-6, TNF-α, and IL-12 production.
Diltiazem downregulates IL-12 production by human dendritic cells / A., D'Ambrosio; BACHETONI ROSSI VACCARI, Alessandra; E., Giacomini; M., Quaranta; F., Quintieri. - In: TRANSPLANTATION PROCEEDINGS. - ISSN 0041-1345. - 33:1-2(2001), pp. 236-239. (Intervento presentato al convegno 18th World Congress of the Transplantation-Society tenutosi a ROME, ITALY nel AUG 27-SEP 01, 2000) [10.1016/s0041-1345(00)01992-8].
Diltiazem downregulates IL-12 production by human dendritic cells
BACHETONI ROSSI VACCARI, Alessandra;
2001
Abstract
It is well known that IL-12 plays a central role in the initiation and control of allogeneic immune response. It promotes the proliferation of lymphocytes and NK cells, cytotoxic activity of NK cells, and CTL. It was recently shown that IL-12 is involved in the regulation of T helper Th1-Th2 responses by exerting stimulatory effects on Th1 and inhibitory effects on Th2. This regulatory role is believed to result from the ability of IL-12 to induce IFN-γ production in activated T cells and NK cells.[1 and 2] Th1 cytokines (IL-2 and IFN-γ) promote both CTL and delayed-type hypersensitivity (DTH) responses, which are considered the principal effector mechanisms of allograft rejection. Diltiazem, a calcium channel blocker used in organ transplantation, is often included in clinical protocols in association with cyclosporin A and corticosteroids.[3] It was used initially because of its antinephrotoxic and antihypertensive effects, so that the undesirable side effects induced by immunosuppressive therapy could be reduced. We previously studied the effect of diltiazem on human mixed lymphocyte reactions (MLR) and on isolated human monocytes, showing the capacity of this drug to affect proinflammatory cytokine production.[4 and 5] Since dendritic cells (DCs) are the most effective antigen-presenting cells (APCs) to prime naive T cells, we were interested in determining the influence of diltiazem on human DCs. Human DCs generated from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) have been characterised as immature DCs. To become fully potent APCs, DCs must undergo maturation induced either by a proinflammatory signal such as lipopolysaccharide (LPS) or by interaction with CD40L expressed on activated T lymphocytes. [6] The ability of mature DCs to act as potent APCs is due to their high expression of MHC and costimulatory molecules and also to their production of cytokines, especially IL-12. Therefore, we determined the effect of diltiazem on cytokine production by human DCs with a particular interest in IL-1β, IL-6, TNF-α, and IL-12 production.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
