Toxicity of OKT3 increases with dosage: a controlled study in renal transplant recipients.
In the present study we prospectively compared side effects occurring in 12 patients after the first administration of low-dose OKT3 (0.5 mg twice daily) induction therapy with those in 10 patients who were treated with a conventional dose of OKT3 (5 mg daily) for acute rejection. We also investigated cytokine release and activation of complement and neutrophils as all of these are held responsible for OKT3-induced side effects. Low-dose OKT3 resulted in a significantly decreased side effects score compared to that after a conventional dose of OKT3 (1.8 vs 5.1, p = 0.0006). Following the first administration of low-dose OKT3, TNF peak levels were significantly lower than after a conventional dose of OKT3. In contrast to our data on conventional dose OKT3 treatment, the first administration of low-dose OKT3 did not induce complement activation as reflected by C3a and C4b/c levels in plasma. Finally, the increase in neutrophil degranulation products lactoferrin and elastase-varies; is directly proportional to 1-antitrypsin was much less following 0.5 mg OKT3 than following 5 mg. We conclude that OKT3-induced toxicity is dose-dependent and is mediated not only by cytokine release but also by activation of complement and neutrophils.
Parlevliet
K J
KJ
Department of Internal Medicine, University of Amsterdam, The Netherlands.
Bemelman
F J
FJ
Yong
S L
SL
Hack
C E
CE
Surachno
J
J
Wilmink
J M
JM
ten Berge
I J
IJ
Schellekens
P T
PT
D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000209:etiology; D006084:Graft Rejection / Q000503:physiopathology / Q000517:prevention & control*; D006261:Headache / Q000209:etiology; D006801:Humans; D016030:Kidney Transplantation; D016853:Muromonab-CD3 / Q000009:adverse effects*; D018375:Neutrophil Activation / Q000187:drug effects; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016853:Muromonab-CD3; D014409:Tumor Necrosis Factor-alpha