Clinical Investigation

Kidney International (1994) 46, 1674–1679; doi:10.1038/ki.1994.467

Pretreatment with divided doses of steroids strongly decreases side effects of OKT3

Frederike J Bemelman1, Saskia Buysmann1, Janto Surachno1, Joep M Wilmink1, Peter Th A Schellekens1 and Ineke J M ten Berge1

1Academic Medical Center, University of Amsterdam, and Department of Internal Medicine, Renal Transplant Unit and Clinical Immunology Unit, Amsterdam, The Netherlands

Correspondence: R J M ten Berge MD PhD, Academic Medical Center, University of Amsterdam, Department of Internal Medicine, Renal Transplant Unit F4-215, PO Box 22700, 1100 DE Amsterdam, The Netherlands.

Received 21 January 1994; Revised 7 July 1994; Accepted 7 July 1994.

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Abstract

Pretreatment with divided doses of steroids strongly decreases side effects of OKT3. The aim of this study was to attenuate side effects of OKT3 by variation of the time interval between administration of corticosteroids and OKT3 in renal allograft recipients. In view of a maximal lymphocytopenia at six hours following MPNS, we postulated a greater preventive action on side effects from administration of methylprednisolone (MPNS) at six hours preceding the first dose of OKT3 compared to administration immediately before. Two groups of renal transplant patients treated for acute rejection with 5 mg OKT3 were studied. Ten patients received 500 mg MPNS six hours and ten patients one hour before administration of OKT3. We measured clinical side effects, body temperature, TNF and IL-6. There were no differences between the two groups regarding clinical side effects and peak body temperatures. However, MPNS administered six hours before administration of OKT3 diminished TNF release; MPNS one hour before decreased IL-6 release. We studied an additional group of six patients receiving 250 mg MPNS six hours before, followed by 250 mg one hour before OKT3. This group experienced significantly less side effects and lower body temperature. In addition, IL-6 levels were significantly decreased. We conclude that two times 250 mg MPNS administered six hours and one hour before the first administration of OKT3 effectively attenuates adverse reactions following administration of OKT3.

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References

  1. Ortho Multicenter Transplant Group: A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. Ortho Multicenter Transplant Study Group. N Engl J Med 313:337–342, 1985
  2. Thisthlethwaite JR, Cosimi AB, Delmonico FL, Rubin RH, Talkoff-Rubin N, Nelson PW, Fang L, Russell PS: Evolving use of OKT3 monoclonal antibody for treatment of renal allograft rejection. Transplantation 38:695–701, 1984
  3. Deierhoi MH, Barber WH, Curtis JJ, Julian B, Luke RG, Hudson S, Barger BO, Diethelm AG: A comparison of OKT3 monoclonal antibody and corticosteroids in the treatment of acute renal allograft rejection. Am J Kidney Dis 11:86–89, 1988 | PubMed |
  4. Norman DJ, Shield CF, Barry J, Bennett WM, Henell K, Kimball J, Funnell B, Hubert B: Early use of OKT3 monoclonal antibody in renal transplantation to prevent reaction. Am J Kidney Dis 11:107–110, 1988
  5. Thisthlethwaite JR, Stuart JK, Mayes JT, Gaber AO, Woodle S, Buckingham MR, Stuart FP: Monitoring and complications of monoclonal therapy. Am J Kidney Dis 11:112–119, 1988
  6. Chatenoud L, Ferran C, Reuter A, Legendre C, Gevaert Y, Kreis H, Franchimont P, Bach J: Systemic reaction to the anti-T-cell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferon-gamma. N Engl J Med 320:1420–1421, 1989 | PubMed | ISI | ChemPort |
  7. Ferran C, Sheehan K, Dy M, Merite S, Schreiber R, Merite S, Landais P, Noel L, Grau G, Bluestone J, Bach J, Chatenoud L: Cytokine-related syndrome following injection of anti-CD3 monoclonal antibody: further evidence for transient in vivo T cell activation. Eur J Immunol 20:509–515, 1990 | PubMed | ISI | ChemPort |
  8. Abramowicz D, Schandene L, Goldman M, Crusiaux A, Vereerstraeten P, De Pauw L, Wybran J, Kinnaert P, Dupont E, Toussaint C: Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. Transplantation 47:606–608, 1989 | PubMed | ISI | ChemPort |
  9. Chatenoud L, Ferran C, Legendre C, Thouard I, Merite S, Reuter A, Gevaert Y, Kreis H, Franchimont P, Bach J: In vivo cell activation following OKT3 administration. Systemic cytokine release and modulation by corticosteroids. Transplantation 49:697–702, 1990 | PubMed | ISI | ChemPort |
  10. Gastron RS, Deierhoi MH, Patterson T, Prasthofer E, Julian BA, Barber WH, Laskow DA, Diethelm AG, Curtis JJ: OKT3 first-dose reaction: Association with T cell subsets and cytokine release. Kidney Int 39:141–148, 1991
  11. Bloemena E, Ten Berge RJM, Surachno S, Wilmink JM: Kinetics of interleukin 6 during OKT3 treatment in renal allograft recipients. Transplantation 50:330–331, 1990
  12. Raasveld MHM, Bemelman FJ, Schellekens PTA, Hack CE, Ten Berge RJM: Complement activation during OKT3 treatment: A possible explanation for respiratory side effects. Kidney Int 43:1140–1149, 1993 | PubMed |
  13. Alegre ML, Vandenabeele P, Depierreux M, Florquin S, Deschodt-Lanckman M, Flamand V, Moser M, Oberdan L, Urbain J, Fiers W, Goldman M: Cytokine release syndrome induced by the 145-2c11 anti-CD3 monoclonal antibody in mice: Prevention by high doses of methylprednisolone. J Immunol 146:1184–1187, 1991 | PubMed | ISI | ChemPort |
  14. Ferran C, Dy M, Merite S, Sheehan K, Schreiber R, Leboulenger F, Landais P, Bluestone J, Bach J, Chatenoud L: Reduction of morbidity and cytokine release in anti-CD3 moab-treated mice by corticosteroids. Transplantation 50:642–648, 1990 | PubMed | ISI | ChemPort |
  15. Peces R, Urra JM, Escalada P, Gorostidi M, Gonzales E, Lopez-L-Arreo C: High-dose methylprednisolone inhibits the OKT3-induced cytokine related syndrome. Nephron 63:118–118, 1993
  16. Chatenoud L, Legendre C, Ferran C, Bach J-F, Kreis H: Corticosteroid inhibition of the OKT3-induced cytokine-related syndrome—Dosage and kinetics prerequisites. Transplantation 51:334–338, 1991 | PubMed | ISI | ChemPort |
  17. Fauci AS, Dale DC: The effect of hydrocortisone on the kinetics of normal human lymphocytes. Blood 46:235–243, 1975 | PubMed | ISI | ChemPort |
  18. Oosterhuis B, Ten Berge RJM, Schellekens PTHA, Van Boxtel CJ: Concentration-dependent effects of prednisolone on lymphocyte subsets and mixed lymphocyte culture in humans. J Pharm Exp Ther 243:716–722, 1987
  19. Ten Berge RJM, Sauerwein HP, Yong SL, Schellekens PTHA: Administration of prednisolone in vivo affects ratio of OKT4/OKT8 and the LDH-isoenzyme pattern of human T lymphocytes. Clin Immunol Immunopathol 30:91–103, 1984 | PubMed | ChemPort |
  20. Rota S, Rambaldi A, Gaspari F, Noris M, Daina E, Benigni A, Perna A, Donadelli R, Remuzzi G, Garattini: Methylprednisolone dosage effects on peripheral subpopulation and eicosanoid synthesis. Kidney Int 42:981–990, 1992 | PubMed | ChemPort |
  21. Claman H: Corticosteroids and lymphoid cells. N Engl J Med 287:388–397, 1972 | PubMed | ChemPort |
  22. Helle M, Boeye L, Groot De E, Vos De A, Aarden LA: Sensitive ELISA for interleukin-6; detection of IL-6 in biological fluids: synovial fluids and sera. J Immunol Methods 138:47–52, 1991 | Article | PubMed | ISI | ChemPort |
  23. Shield CF, Kahana L, Pirsch J, Vergne-Marini P, First MR, Schroeder TJ, Cohen D, Norman DJ, Monaco A, Martinez A, Dinarello CA, Dehlinger J, Wu SH, Van Horn A: Use of indomethacin to minimize the adverse reactions associated with orthoclone OKT3 treatment of kidney allograft rejection. Transplantation 54:164–165, 1992
  24. Chan GL, Weinstein SS, Wright CE, Bowers VD, Alveranga DY, Shires DL, Ackermann JR, Lefor W, Kahana L: Encephalopathy associated with OKT3 administration; possible interaction with indomethacin. Transplantation 52:148–150, 1991 | PubMed |
  25. Alegre ML, Gastaldello K, Abramowicz D, Kinnaert P, Vereer-Straeten P, De Pauw L, Vandenbeele P, Moser M, Oberdan L, Goldman M: Evidence that pentoxifylline reduces anti-CD3 monoclonal antibody-induced cytokine release syndrome. Transplantation 52:674–679, 1991
  26. Charpentier B, Hiesse C, Lantz O, Ferran C, Stephens S, O'Shaugnessy D, Bodmer M, Benoit G, Bach J, Chatenoud L: Evidence that antihuman tumor necrosis factor monoclonal antibody prevents OKT3-induced acute syndrome. Transplantation 54:997–1002, 1992 | PubMed | ISI | ChemPort |
  27. Goldman M, Abramowicz D, De Pauw L, Alegre M, Widera I, Vereerstraeten P, Kinnaert P: OKT3-induced cytokine release attenuation by high-dose methylprednisolone letter. Lancet 2:802–803, 1989
  28. Fauci AS, Dale DC: The effect of in vivo hydrocortisone on subpopulations of human lymphocytes. J Clin Invest 53:240–246, 1974 | PubMed | ChemPort |
  29. Waage A, Bakke O: Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunol 63:299–302, 1988
  30. Beutler B, Krochin N, Milsark IW, Luedke C, Cerami A: Control of cachectin (tumor necrosis factor) synthesis: Mechanism of endotoxin resistance. Science 232:977–980, 1986 | Article | PubMed | ISI | ChemPort |
  31. Grattage LP, Mckenzie IFC, Hogarth PM: Effects of PMA, cytokines and dexamethasone on the expression of cell surface Fc receptors and mRNA in U937 cells. Immunol Cell Biol 70:97–105, 1992
  32. Duits AJ, Aarden LA, Ernst LK, Capel PJA, Van De Winkel JGJ: Isotype-specific cross-linking of select human FcgammaR isoforms triggers release of IL-6. Clin Exp Immunol 92:225–231, 1993
  33. Hirooka Y, Mitsuma T, Nogimori T, Ishizuki Y: Effect of hydrocortisone on interleukin-6 production in human peripheral blood mononuclear cells. Mediators Inflam 1:9–13, 1992
  34. Barber AE, Coyle SM, Marano MA, Fischer E, Calvano SE, Fong Y, Moldawer LL, Lowry SF: Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man. J Immunol 150:1999–2006, 1993
  35. Weber J, Yang JC, Topalian SL, Parkinson DR, Schwartzentruber DS, Ettinghausen SE, Gunn H, Mixon A, Kim H, Cole D, Levin R, Rosenberg SA: Phase I trial of subcutaneous interleukin-6 in patients with advanced malignancies. J Clin Oncol 11:499–506, 1993 | PubMed | ISI | ChemPort |
  36. Charpentier B, Hiesse C, Lantz O, Ferran C, Stephens S, O'Shougnessy D, Bodmer JF, Chatenoud L: Evidence that antihuman tumor necrosis factor monoclonal antibody prevents OKT3-induced acute syndrome. Transplantation 54:997–1002, 1992 | PubMed | ISI | ChemPort |
  37. Matthys P, Dillen C, Proost P, Heremans H, Van Damme J, Billiau A: Modification of the anti-CD3-induced cytokine release syndrome by anti-interferon-gamma or anti-interleukin-6 antibody treatment: protective effects and biphasic changes in blood cytokine levels. Eur J Immunol 23:2209–2216, 1993

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