Induction of tumor necrosis factor-α 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-1 beta (IL-1 beta), 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-1 beta 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-1 beta and TGF-beta deserve further study. (C) 1998 American Cancer Society.