Peripheral natural killer cell activity and intraperitoneal soluble p55 tumor necrosis factor receptor in patients with malignant ascites: two possible indicators for response to intraperitoneal combined tumor necrosis factor α and interferon γ treatment |
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Authors: | Marion-Gabriele Ott Daniela N Männel Harald Gallati Matthias Goerig Ulrich Raeth |
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Institution: | H?matologie, Zentrum der Inneren Medizin III, Johann-Wolfgang-Goethe-Universit?t Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Deutschland, DE Tumorimmunologie, Institut für Pathologie, Universit?t Regensburg, Franz-Josef-Strauss-Allee, D-93042 Regensburg, Deutschland, DE Hoffmann La Roche AG, Basel, Schweiz, CH Medizinische Universit?tsklinik, Universit?t Erlangen-Nürnberg, Deutschland, DE Medizinische Universit?tsklinik IV, Universit?t Heidelberg, Bergheimer Strasse 58, D-69115 Heidelberg, Deutschland, DE
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Abstract: | Tumor necrosis factor α (TNFα) and interferon γ (IFNγ) are important immunomodulators. They are capable of acting in a synergistic
manner on tumor cells in vitro and in vivo. In a clinical phase I study 13 patients with malignant ascites due to abdominal
spread of different primary tumors received intraperitoneally (i. p.) TNFα and IFNγ once weekly over 3 – 8 weeks in order
to evaluate the effect of locoregionally administered TNFα/IFNγ on ascites formation. Therefore some peripheral and local
immunological functional parameters of peripheral blood and malignant ascites were investigated. Mononuclear lymphocytes and
natural killer (NK) cell activity of peripheral blood and ascites, TNF-inhibitory activity, soluble p55 and p75 TNF receptors,
and prostaglandin E2 values in ascites were measured immediately before and 24 h after each TNFα/IFNγ infusion. Peripheral mononuclear lymphocytes
and NK activity decreased significantly 24 h after i. p. TNFα/IFNγ application. However, over the entire treatment schedule,
peripheral NK activity in all responders showed a continuous increase, when compared to pre TNFα/IFNγ treatment levels. In
contrast, NK activity in non-responders constantly decreased. In contrast to non-responders, TNF-inhibitory activity and soluble
p55 TNF receptor levels, determined in ascites, decreased in responders. Taken together, our findings suggest, that successful
locoregional i. p. TNFα/IFNγ therapy induces systemic immunological reactions possibly after saturation of soluble p55 TNF
receptors in ascites, which leads to an increase of peripheral NK activity.
Received: 28 September 1995 / Accepted: 16 November 1995 |
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Keywords: | Tumor necrosis factor α Interferon γ NK cell activity Soluble TNF receptors Malignant ascites |
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