Title
Evidence that pentoxifylline reduces anti-cd3 monoclonal antibody-induced cytokine release syndrome Evidence that pentoxifylline reduces anti-cd3 monoclonal antibody-induced cytokine release syndrome
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Baltimore, Md ,
Subject
Human medicine
Source (journal)
Transplantation. - Baltimore, Md, 1963, currens
Volume/pages
52(1991) :4 , p. 674-679
ISSN
0041-1337
ISI
A1991GK37800018
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Pretreatment with pentoxifylline (PTX), a methylxanthine known for its beneficial effects on tissue lesions induced by the injection of endotoxin or recombinant cytokines, was shown to decrease the systemic release of tumor necrosis factor and interleukin 2 occurring after the administration of the anti-CD3 monoclonal antibody 145-2C11 in mice. In parallel, PTX attenuated the hypothermia and the rise in blood urea nitrogen observed in this model. The protective effect of PTX on the toxicity of 145-2C11 was confirmed by the reduction of the mortality among D-galactosamine-sensitized animals. The mitigation by PTX of the release of cytokines did not affect the immunosuppression entailed by 145-2C11 as assessed by the unmodified cytotoxic T lymphocytes (CTL) unresponsiveness against alloantigens measured 48 hr after the injection of the mAb. In vitro experiments on human peripheral blood leukocytes indicated that PTX alone or in synergy with methylprednisolone (m-PDS) also inhibited the release of TNF and IL-2 induced by OKT3. Finally, in a preliminary pilot trial conducted in kidney transplant recipients, we observed that pretreatment with PTX (20 mg/kg i.v.) in addition to m-PDS (2 g i.v.) reduced by half the amount of TNF released in the blood stream after the first injection of OKT3, while no further reduction of the low levels of IL-2 was found.
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