Induction of tumor necrosis factor-alpha as a cause of bleomycin-related toxicity.
BACKGROUND
The application of bleomycin is characterized by acute side effects, such as fever, chills, and sometimes hypotension and tachypnea. Furthermore, bleomycin is known to induce pneumonitis. There are several indications that the induction of cytokines by bleomycin is involved in the development of these side effects.


METHODS
In this study, the authors determined the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and transforming growth factor-beta (TGF-beta) before and after bleomycin infusion in 14 patients treated for disseminated nonseminomatous germ cell tumor.


RESULTS
Compared with the pretreatment value, TNF-alpha was significantly increased 3, 4.5, and 24 hours after bleomycin infusion. For IL-1beta and TGF-beta, no significant alterations were observed within 24 hours after administration of bleomycin.


CONCLUSIONS
The increase in TNF-alpha after administration of bleomycin suggests a role for this cytokine in the development of the acute side effects and probably also in the occurrence of bleomycin-induced pulmonary toxicity. The involvement of IL-1beta and TGF-beta deserve further study.
Sleijfer
S
S
Department of Medical Oncology, University Hospital, Groningen, The Netherlands.
Vujaskovic
Z
Z
Limburg
P C
PC
Schraffordt Koops
H
H
Mulder
N H
NH
D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D001761:Bleomycin / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D018237:Germinoma / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D000964:Antimetabolites, Antineoplastic; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin