Intrapleural interleukin-2 induces nitric oxide production in pleural effusions from malignant mesothelioma: a possible mechanism of interleukin-2-mediated cytotoxicity?
Due to the frequent use of intrapleural interleukin-2 (IL-2) to treat pleural effusions from malignant mesothelioma (MMe), we measured nitric oxide (NO) end product nitrite (NO(2)(-)) in pleural effusions of 12 MMe patients with chronic or chronic-relapsing pleurisy. Through high performance liquid chromatography analysis, NO(2)(-) was found in the initial pleural fluid sample of all patients (156.25 pmol ml(-1)), and increased significantly following IL-2 intrapleural instillation, both at 24 (589.91 pmol ml(-1), P < or = 0.0005) and 48 h (756 pmol ml(-1), P< or = 0.0005). Even though it is difficult to argue if the large amounts of NO end product NO(2)(-) we observed is produced by IL-2-stimulated and recruited immune cells, by MMe cells themselves, or by both, it is possible that NO could contribute to the complex antitumor activity of IL-2.
Porta
Camillo
C
Internal Medicine and Medical Oncology, IRCCS San Matteo University Hospital, I-27100 Pavia, Italy. c.porta@smatteo.pv.it
Rizzo
Vittoria
V
Zimatore
Matteo
M
Sartore-Bianchi
Andrea
A
Danova
Marco
M
Mutti
Luciano
L
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D009573:Nitrites / Q000032:analysis*; D010996:Pleural Effusion / Q000188:drug therapy* / Q000209:etiology*
D000970:Antineoplastic Agents; D007376:Interleukin-2; D009573:Nitrites; D009569:Nitric Oxide