Intrapleural instillation of interferon γ in patients with malignant pleurisy due to lung cancer

Abstract

The effect of intrapleural instillation of recombinant human interferon γ (IFNγ) at increasing doses of (1–12) × 10⁶ U was examined in six patients with cytologically positive pleural effusion due to lung cancer. Intrapleural instillation was repeated up to three times. Clinically, no reaccumulation of pleural effusion was observed in one patient and disappearance of lung cancer cells from the pleural effusion was seen in two other patients. No severe side-effects were observed. Considerable levels of IFNγ remained in the pleural effusion as well as in patients’ serum up to 7 days after instillation of 2 × 10⁶ U and higher doses. The total cell number showed a transient decrease on day 1 of therapy. Levels of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin(IL)-1β and IL-6, in the pleural effusion remained almost stable after IFNγ instillation. On the other hand, intrapleural IL-1 receptor antagonist levels were remarkably elevated by the instillation of IFNγ. IL-2- and IL-12-inducible killer activity of pleural mononuclear cells tended to increase slightly. Despite the inability of IFNγ to control pleural effusion in this treatment schedule, IFNγ instilled by an intrapleural route had a potential local antitumor activity. Moreover, since IFNγ persists in pleural effusions for a long time after a single instillation, such a therapy in combination with other fibrogenic biological response modifiers can be promising.