INCREASED DERMAL EXPRESSION OF ICAM-1 AND VCAM-1 AFTER ADMINISTRATIONOF 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 vascul ar endothelium, To investigate the effects of OKT3 induced cytokine re lease on endothelial- and lymphocyte adhesion molecule expression in v ivo, we studied sequential skin biopsies of six renal allograft recipi ents treated for acute rejection with 5 mg OKT3, An additional group o r six patients treated for acute rejection with 500 mg methylprednisol one served as a control group. Compared to pre-treatment biopsies, bio psies taken 4.5- and 24 hours after the first OKT3 dose showed a maxim al increase in VCAM-1 and ICAM-1 expression, respectively. Ln parallel , an increased number of CD2(+), CD11a(+), and CD49d(+) mononuclear ce lls in the skin was observed in all OKT3 treated patients. No changes were observed after methylprednisolone treatment. Pie conclude that th e OKT3 induced cytokine release Induces increased ICAM-1- and VCAM-1 e xpression on vascular endothelium,leading to increased influx of CD2() lymphocytes which may contribute to the peripheral lymphocytopenia a fter OKT3.