Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients.
OKT3 , a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFalpha and IL1beta. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance. We sought to analyze the role of proinflammatory and Th-1 cytokines in T cell recovery and rejection after liver transplantation with OKT3 prophylaxis. In plasma samples from 32 patients, we measured TNFalpha, IL1beta and IL6 (before transplant and on postoperative days 1, 2 and 3) and IL2, IFNgamma, sIL2R and slCAM (postoperative days 5, 7 and 10) and examined possible correlations with T-cell recovery and occurrence of rejection within 3 weeks. TNFalpha, IL1beta, and IL6 did not correlate with T-cell recovery. In patients who rejected, IL2 and IFNgamma on postoperative days 5 and 7 correlated with degree of T-cell recovery by day 10; a significant rise in sIL2R over time also correlated with T-cell recovery in this group. Our results emphasize the role of Th-1 cytokines in rejection following OKT3 induction and suggest that markers of T cell activation may predict risk.
Roayaie
S
S
The Recanati/Miller Transplantation Institute, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Sheiner
P A
PA
Emre
S
S
Guy
S
S
Schwartz
M E
ME
Boros
P
P
Miller
C M
CM
D000818:Animals; D016207:Cytokines / Q000097:blood*; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D016853:Muromonab-CD3; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma