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 of six patients treated for acute rejection with 50 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. In 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. We 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.
Buysmann
S
S
University of Amsterdam, Department of Internal Medicine, The Netherlands.
van Diepen
F N
FN
Surachno
S
S
Pals
S T
ST
ten Berge
R J
RJ
D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D001665:Binding Sites; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*; D016030:Kidney Transplantation; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000139:chemically induced / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*
D015703:Antigens, CD; D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008775:Methylprednisolone