Increased dermal expression of ICAM-1 and VCAM-1 after administration of OKT3 in man

OKT3 induces a systemic release of cytokines and a profound peripheral lymphocytopenia. In vitro, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma increase adhesion molecule expression on vascular endothelium, To investigate the effects of OKT3 induced cytokine release on endothelial- and lymphocyte adhesion molecule expression in vivo, we studied sequential skin biopsies of six renal allograft recipients treated for acute rejection with 5 mg OKT3, An additional group or six patients treated for acute rejection with 500 mg methylprednisolone served as a control group. Compared to pre-treatment biopsies, biopsies taken 4.5- and 24 hours after the first OKT3 dose showed a maximal increase in VCAM-1 and ICAM-1 expression, respectively. Ln parallel, an increased number of CD2(+), CD11a(+), and CD49d(+) mononuclear cells in the skin was observed in all OKT3 treated patients. No changes were observed after methylprednisolone treatment. Pie conclude that the OKT3 induced cytokine release Induces increased ICAM-1- and VCAM-1 expression on vascular endothelium,leading to increased influx of CD2(+) lymphocytes which may contribute to the peripheral lymphocytopenia after OKT3.