Intrapleural interleukin-2 induces nitric oxide production in pleural effusions from malignant mesothelioma: a possible mechanism of interleukin-2-mediated cytotoxicity?

Our plain-English summary of Intrapleural interleukin-2 induces nitric oxide production in pleural effusions from malignant mesothelioma: a possible mechanism of interleukin-2-mediated cytotoxicity?, by C. Porta, V. Rizzo, M. Zimatore, et al (Lung Cancer, 2002).

The study

• Authors: C. Porta, V. Rizzo, M. Zimatore, A. Sartore-Bianchi, M. Danova, L. Mutti
• Journal: Lung Cancer
• Published: 2002;38(2):159-62
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

Copyright 2002 Elsevier Science Ireland Ltd.

In plain English

This small clinical study from Italy measured nitrite, a breakdown product of nitric oxide, in the chest fluid of 12 patients (5 men and 7 women, aged 50 to 68) with advanced pleural malignant mesothelioma and fluid buildup around the lung that was long-lasting or kept coming back. Patients received recombinant interleukin-2 (IL-2), an immune-system protein, placed directly into the chest cavity: 9 million units on two consecutive days weekly, up to eight doses. Nitrite was found in the first fluid sample of every patient, averaging 156.25 pmol per ml. It rose to a mean of 589.91 pmol per ml at 24 hours and 756 pmol per ml at 48 hours, an increase the authors reported as statistically significant. The article describes the exact sampling times inconsistently. Nitrite levels did not differ significantly between the 4 patients with a complete response and the 8 with a partial response. The authors said they could not tell whether the nitric oxide came from immune cells, tumor cells or both. They concluded it is possible that nitric oxide contributes to IL-2's anti-tumor activity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Small clinical study with no comparison group. Nitrite was measured in each patient's pleural fluid before and after intrapleural IL-2 treatment.
• Who was studied: 12 patients (5 males and 7 females, aged 50 to 68, average 64.9 years) with advanced (stage III or IV) pleural malignant mesothelioma and chronic or chronic-relapsing pleurisy. All had been treated before. Tumor types were 8 epithelioid, 2 sarcomatoid and 2 mixed. The authors worked at hospitals in Pavia, Italy. The article does not give study dates.
• Exposure: Intrapleural recombinant interleukin-2, 9 MU per instillation, given on two consecutive days weekly for a maximum of eight administrations (4 weeks). The article does not discuss asbestos exposure.
• Main results:
  • Before treatment, nitrite was present in the pleural fluid of all 12 patients. The mean was 156.25 pmol per ml (standard deviation 28.76, median 151.5, range 121 to 215).
  • At 24 hours, mean nitrite rose to 589.91 pmol per ml (standard deviation 89.76, median 595.5, range 437 to 721).
  • At 48 hours, mean nitrite rose to 756 pmol per ml (standard deviation 72.05, median 783.5, range 610 to 836).
  • The authors reported the increases at both 24 and 48 hours as statistically significant. The P value is printed as 0.0005, but the comparison symbol before it is garbled in this text.
  • Nitrite levels did not differ significantly between patients with a complete response and patients with a partial response.
  • Nitrite levels showed no statistically significant correlation with the total amount of pleural fluid.
  • All 12 patients responded after an average of 5.83 IL-2 administrations. The response was complete in 4 patients (33.3%) and partial in 8 (66.6%).
  • All patients had pain. Fever was grade I in 9 patients (75%) and grade II in 3 patients (25%). No other toxicities were recorded.
• The authors' conclusion: The authors concluded it is possible that nitric oxide could contribute to the anti-tumor activity of IL-2.
• Limitations the authors state:
  • The authors stated it is difficult to tell whether the nitric oxide came from IL-2-stimulated immune cells, from the mesothelioma cells themselves, or from both.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Malignant Mesothelioma, Pleurisy.

Related studies

• Mechanisms of asbestos-induced nitric oxide production by rat alveolar macrophages in inhalation and in vitro models — T.R. Quinlan, K.A. BeruBe, et al. (1998)
• Asbestos redirects nitric oxide signaling through rapid catalytic conversion to nitrite — D.D. Thomas, M.G. Espey, et al. (2006)
• Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis — H. Ohshima, H. Bartsch (1994)
• Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages — G. Thomas, T. Ando, et al. (1994)
• Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes — T. Nishiike, Y. Nishimura, et al. (2005)
• Progress report on the palliative therapy of 100 patients with neoplastic effusions by intracavitary low-dose interleukin-2 — P. Lissoni, M. Mandalà, et al. (2001)

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