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. 2000;9(3-4):141–146. doi: 10.1080/09629350020002877

Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients.

S Roayaie 1, P A Sheiner 1, S Emre 1, S Guy 1, M E Schwartz 1, P Boros 1, C M Miller 1
PMCID: PMC1781756  PMID: 11132770

Abstract

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.

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Selected References

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  1. Emre S., Schwartz M. E., Mor E., Kishikawa K., Yagmur O., Thiese N., Sheiner P., Jindal R. M., Chiodini S., Miller C. M. Obviation of prereperfusion rinsing and decrease in preservation/reperfusion injury in liver transplantation by portal blood flushing. Transplantation. 1994 Mar 27;57(6):799–803. doi: 10.1097/00007890-199403270-00004. [DOI] [PubMed] [Google Scholar]
  2. Ferran C., Sheehan K., Dy M., Schreiber R., Merite S., Landais P., Noel L. H., Grau G., Bluestone J., Bach J. F. Cytokine-related syndrome following injection of anti-CD3 monoclonal antibody: further evidence for transient in vivo T cell activation. Eur J Immunol. 1990 Mar;20(3):509–515. doi: 10.1002/eji.1830200308. [DOI] [PubMed] [Google Scholar]
  3. Greig P. D., Woolf G. M., Sinclair S. B., Abecassis M., Strasberg S. M., Taylor B. R., Blendis L. M., Superina R. A., Glynn M. F., Langer B. Treatment of primary liver graft nonfunction with prostaglandin E1. Transplantation. 1989 Sep;48(3):447–453. doi: 10.1097/00007890-198909000-00020. [DOI] [PubMed] [Google Scholar]
  4. Hoffmann M. W., Wonigeit K., Steinhoff G., Herzbeck H., Flad H. D., Pichlmayr R. Production of cytokines (TNF-alpha, IL-1-beta) and endothelial cell activation in human liver allograft rejection. Transplantation. 1993 Feb;55(2):329–335. doi: 10.1097/00007890-199302000-00019. [DOI] [PubMed] [Google Scholar]
  5. Marlin S. D., Staunton D. E., Springer T. A., Stratowa C., Sommergruber W., Merluzzi V. J. A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection. Nature. 1990 Mar 1;344(6261):70–72. doi: 10.1038/344070a0. [DOI] [PubMed] [Google Scholar]
  6. McDiarmid S. V., Millis M. J., Terasaki P. I., Ament M. E., Busuttil R. W. OKT3 prophylaxis in liver transplantation. Dig Dis Sci. 1991 Oct;36(10):1418–1426. doi: 10.1007/BF01296809. [DOI] [PubMed] [Google Scholar]
  7. Odum N., Kanner S. B., Ledbetter J. A., Svejgaard A. MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors. J Immunol. 1993 Jun 15;150(12):5289–5298. [PubMed] [Google Scholar]
  8. Platz K. P., Mueller A. R., Rossaint R., Steinmüller T., Lemmens H. P., Lobeck H., Neuhaus P. Cytokine pattern during rejection and infection after liver transplantation--improvements in postoperative monitoring? Transplantation. 1996 Nov 27;62(10):1441–1450. doi: 10.1097/00007890-199611270-00011. [DOI] [PubMed] [Google Scholar]
  9. Ploeg R. J., D'Alessandro A. M., Knechtle S. J., Stegall M. D., Pirsch J. D., Hoffmann R. M., Sasaki T., Sollinger H. W., Belzer F. O., Kalayoglu M. Risk factors for primary dysfunction after liver transplantation--a multivariate analysis. Transplantation. 1993 Apr;55(4):807–813. doi: 10.1097/00007890-199304000-00024. [DOI] [PubMed] [Google Scholar]
  10. Rubin L. A., Jay G., Nelson D. L. The released interleukin 2 receptor binds interleukin 2 efficiently. J Immunol. 1986 Dec 15;137(12):3841–3844. [PubMed] [Google Scholar]
  11. Sheiner P. A., Guarrera J. V., Grunstein E., Emre S., Guy S. R., Schwartz M. E., Miller C. M., Boros P. Increased risk of early rejection correlates with recovery of CD3 cell count after liver transplant in patients receiving OKT3 induction. Transplantation. 1997 Oct 27;64(8):1214–1216. doi: 10.1097/00007890-199710270-00026. [DOI] [PubMed] [Google Scholar]
  12. Sutherland F. R., Aboujaoude M., White M. J., Yamada J., Ghent C., Grant D., Wall W., Garcia B., Mazaheri R., Lazarovits A. I. Mechanisms of rejection during OKT3 therapy: propagation and characterization of CD3 resistant allospecific cytotoxic T cells from a rejecting liver allograft. Clin Immunol Immunopathol. 1991 Jul;60(1):40–54. doi: 10.1016/0090-1229(91)90110-v. [DOI] [PubMed] [Google Scholar]
  13. Tilg H., Vogel W., Aulitzky W. E., Herold M., Königsrainer A., Margreiter R., Huber C. Evaluation of cytokines and cytokine-induced secondary messages in sera of patients after liver transplantation. Transplantation. 1990 Jun;49(6):1074–1080. doi: 10.1097/00007890-199006000-00009. [DOI] [PubMed] [Google Scholar]

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