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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.

Recombinant human interleukin 1β (IL 1β) inhibits growth of B16 melanoma in syngeneic C57BL/6 mice in a dose-dependent manner when given intratumorally, intradermally, or intramuscularly over a period of 5 to 7 days. Inhibition of tumor growth was rapid and measurable within 3 days after the initial injection and occurred regardless of the route of injection. However, only intratumoral (ITU) injections of IL 1β resulted in greater than 90% inhibition in tumor growth. This enhanced inhibition of tumor growth was not dependent on T or NK cells since inhibition of tumor growth occurred in nude and Beige mice. Also, a profound lymphopenia occurred in mice receiving IL 1β. Inhibition of tumor growth did correlate with an increase in the number of polymorphonuclear leukocytes (PMN's) in the circulation. However, only ITU injections of IL 1β increased the number of PMN's within the tumors. IM injections of IL 1β, while increasing the number of PMN's in the circulation, did not increase the influx of PMN's into the tumors. Furthermore, the transfer of PMN's directly into B16 tumors caused a 49% reduction in tumor growth without the presence of IL 1β. These results suggest that in vivo, PMN's may effectively control the growth of tumors and that IL 1β may increase this effectiveness by increasing the number of PMN's in the circulation and by locally stimulating the production of chemotactic factors for PMN's within the tumor.