当前位置： SCI文献检索 > JOURNAL OF CLINICAL IMMUNOLOGY期刊下所有文献 > Induction of circulating tumor necrosis factor (TNF alpha) as the mechanism for the febrile response to interleukin-2 (IL-2) in cancer patients.

Induction of circulating tumor necrosis factor (TNF alpha) as the mechanism for the febrile response to interleukin-2 (IL-2) in cancer patients.

Abstract：

:Fever is frequently observed in cancer patients treated with high-dose recombinant human interleukin-2 (rIL-2). The preincubation of rIL-2 with polymyxin B, an antibiotic that inhibits the biologic effects of endotoxins, did not diminish the pyrogenicity of IL-2 in New Zealand rabbits, indicating that IL-2-induced fever is not due to contaminating endotoxins. In contrast to interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon alpha, which cause fever through their effects on arachidonic acid metabolism in the hypothalamus, IL-2 was unable to induce prostaglandin E2 synthesis in hypothalamic cells or fibroblasts in vitro, suggesting that IL-2 is not intrinsically pyrogenic. To determine if IL-2-induced fever is mediated indirectly through the generation of pyrogenic cytokines, culture supernatants from IL-2-stimulated human peripheral blood mononuclear cells were screened for the presence of pyrogens by direct injection into rabbits and by measuring the amounts of IL-1 alpha, IL-1 beta, and TNF alpha by specific radioimmunoassays (RIA). All three cytokines were readily detected by RIA in these supernatants, which in turn caused fever when injected into rabbits. Furthermore, in six of six cancer patients treated with rIL-2, elevated levels of TNF alpha were detected in the plasma by RIA 2 hr after IL-2 administration. Plasma TNF levels increased from pretreatment values of 14 +/- 7 to 765 +/- 150 pg/ml 2 hr after an IL-2 injection. These results strongly implicate IL-2-induced pyrogenic cytokines, in particular TNF alpha, as a major cause of the fever and possibly other aspects of the acute-phase response associated with IL-2 therapy.

journal_name

J Clin Immunol

journal_title

Journal of clinical immunology

authors

Mier JW,Vachino G,van der Meer JW,Numerof RP,Adams S,Cannon JG,Bernheim HA,Atkins MB,Parkinson DR,Dinarello CA

doi

10.1007/BF00916947

subject

Has Abstract

pub_date

1988-11-01 00:00:00

pages

426-36

issue

6

eissn

0271-9142

issn

1573-2592

journal_volume

8

pub_type

杂志文章

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