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Inhibition of antigen‐presenting cell function by alendronate in vitro
Author(s) -
Sansoni Paolo,
Passeri Giovanni,
Fagi Francesco,
Mohagheghpour Nahid,
Snelli Gianluca,
Brianti Vincenzo,
Engleman Edgar G.
Publication year - 1995
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650101115
Subject(s) - bone resorption , cytokine , peripheral blood mononuclear cell , antigen , immune system , t cell , monocyte , tumor necrosis factor alpha , antigen presentation , chemistry , immunology , medicine , in vitro , biochemistry
Bisphosphonates are potent inhibitors of bone resorption in vivo and are emerging as important and widely used drugs for the treatment of a variety of abnormal bone resorptive processes. In the current study we investigated the in vitro effects of 4‐amino‐1‐hydroxybutylidene‐1,1‐bisphosphonate (alendronate), a recently developed, extremely potent bisphosphonate, on the immune functions of human peripheral blood mononuclear cells (PBMCs). PBMC proliferation induced by lectins, alloantigens, and a nominal antigen (tetanus toxoid) was inhibited in a dose‐dependent manner by alendronate. Pretreatment of monocytes, but not T cells, with the compound at concentrations ranging from 10 −4 to 10 −8 M was inhibitory, indicating that alendronate acts selectively on antigen‐presenting cells (APCs). Alendronate did not affect the viability of monocytes or T cells or the expression of cell surface molecules known to play critical roles in antigen presentation. Alendronate exhibited dose‐dependent inhibition of the production of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) by activated monocytes. The inhibitory effect of 10 −6 M alendronate on PBMC proliferation was reversed by 10 U/ml recombinant rIL‐1β, whereas other cytokines such as IL‐6, TNF‐α, and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) had no effect. Thus, alendronate acts on monocytes to inhibit their antigen‐presenting/accessory cell functions through a mechanism that can be overcome by exogenous IL‐1. The inhibitory effect of this agent on cytokine production may contribute to its inhibitory effect on bone resorption.