Cytokines, adhesion molecules (E-selectin and VCAM-1) and graft-versus-host disease

Analysis of skin biopsy specimens for the presence of adhesion molecules, composition of cellular infiltrates, Ki-67 antigen expression, and examination of serum for interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels, wes performed in patients after allogeneic bone marrow transplantation (alloBMT), to study the pathomechanism of acute graft-versus-host disease (aGvHD). It was found that: 1) early hematological recovery constitutes a risk factor for grade IV GvHD, 2) vascular cell adhesion molecule-1 (VCAM-1) is present in the matrix organizing the cells in the bone marrow and in aGvHD infiltrates, 3) HLA DR antigens aberrant expression in epithelial cells, as well as 4) strong expression of Ki-67 is seen in early stages of aGvHD. These immunopathomorfological lesions are cytokine-dependent. High levels of IL-6 and TNF-alpha were found in sera of patients affected with the aGvHD process and infectious complications. An increase of IL-6 in the course of aGvHD is a sign of poor prognosis. These data support the notion that cytokines facilitate the cell accumulation at the site of aGvHD at the beginning of this process and again, at the final stage of the disease, cytokines high levels are associated with the organ damage.