Oral administration of azithromycin to recipient mice for 5 days during major-histoincompatible BMT suppressed lethal GVHD selleckchem significantly, whereas ex-vivo lymphocyte function was not affected by the drug. These data suggest that azithromycin has potential as a novel prophylactic drug for lethal GVHD. Haematopoietic stem cell transplantation from an allogeneic donor provides curative therapy

for patients with malignant and non-malignant haematological diseases. However, acute graft-versus-host disease (GVHD) is still a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). GVHD is initiated by donor T lymphocytes that recognize host histocompatibility antigens that distinguish host from this website donor. To date, most therapeutic approaches designed to attenuate GVHD have focused on suppressing donor T lymphocytes

[1-5]. These approaches, however, often result in incomplete GVHD attenuation, especially in histoincompatible transplants. Recent murine studies have shown that interactions between donor T lymphocytes and host antigen-presenting cells (APCs) are essential for triggering GVHD [6-11]. Dendritic cells (DCs) derived from haematopoietic stem cells are distributed ubiquitously in blood, lymphoid and peripheral tissues and play important roles in the immune system by stimulating naive T lymphocytes and secreting cytokines that initiate the immune response [12]. The state of DC maturation influences their functions. Various factors, including bacteria-derived antigens such as Metformin price lipopolysaccharide (LPS), viral products, inflammatory cytokines and conditioning regimens such as total body irradiation (TBI) can induce maturation of DCs, which is characterized by up-regulation of major histocompatibility complex (MHC) class II, co-stimulatory molecules and essential chemokine receptors.

Mature DCs (mDCs) promote antigen-specific T cell activation and proliferation. Moreover, following CD40 ligation or Toll-like receptor ligation, mDCs secrete interleukin (IL)-12 p70, which induces interferon (IFN)-γ-producing T helper type 1 (Th1) cells that are considered a pivotal pathogenic factor in acute GVHD [12-15]. Nuclear factor (NF)-κB is a rapid response transcription factor in various cells involved in immune and inflammatory reactions and exerts its effect by inducing expression of cytokines, chemokines, cell adhesion molecules and growth factors [16, 17]. NF-κB is sequestered normally in the cytoplasm of non-stimulated cells and is translocated into the nucleus in response to a variety of stimuli, such as bacterial lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-α. Because it also plays a crucial role in DC maturation [18, 19], NF-κB in DCs might be a rational target for preventing GVHD.