Symptomatic Treatment of Recurrent Malignant Pleural Effusions with Intrapleurally AdministeredCorynebacterium parvum

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Abstract
Intrapleural injection of Corynebacterium parvum (CBP) has been recently proposed as a useful symptomatic treatment of recurrent malignant effusions. Although the result is often a fibrotic thickening of the pleura, CBP is thought to stimulate the effector cells present in the effusion and, possibly, to activate the antitumor cytotoxic activity of the pleural fluid mononuclear cells. To test this hypothesis, we studied 7 patients with recurrent malignant pleural effusions caused by lung cancer and evaluated the cellular composition, the proportions of lymphocyte subpopulations, and the cytotoxic activity of mononuclear cells in the pleural fluid before and 7 days after injection of CBP in the pleural space. The CBP treatment induced a marked decrease in the rate of accumulation of pleural fluid (p < 0.01) and in the concentration of immune effector cells in the pleural exudate (p < 0.001). These changes were associated with a decrease in the percentages of pleural fluid monocytes and lymphocytes present (p < 0.01, each comparison) and to a marked increase in the percentages of pleural fluid neutrophils (p < 0.001). No significant changes in the proportions of T- and B-lymphocytes or in the proportions of helper/inducer and suppressor/cytotoxic T-cells or of natural killer cells were observed in the pleural exudate after CBP treatment (p > 0.2, each comparison). In addition, the cytotoxic activity of pleural fluid mononuclear cells was similar before and after CBP treatment (p > 0.2), and the levels of interferon, as a marker of immunoactivation of mononuclear cells, were not changed after treatment (p > 0.2). Thus, intrapleurally administered CBP is an effective approach to the symptomatic treatment of recurrent malignant pleural effusions; clinical response, however, does not seem to be associated to enhancement Of local cellular immunity.