Eosinophil colony-stimulating factor induced by administration of interleukin-2 into the pleural cavity of patients with malignant pleurisy

Our plain-English summary of Eosinophil colony-stimulating factor induced by administration of interleukin-2 into the pleural cavity of patients with malignant pleurisy, by Y. Nakamura, T. Ozaki, H. Yanagawa, et al (American Journal of Respiratory Cell and Molecular Biology, 1990).

The study

• Authors: Y. Nakamura, T. Ozaki, H. Yanagawa, S. Yasuoka, T. Ogura
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1990;3(4):291-300
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Systemic administration of interleukin (IL)-2 to patients with malignant diseases induces peripheral eosinophilia. In the present study, to clarify the mechanism of eosinophilia induced by IL-2, we examined the changes in the number of eosinophils and eosinophil colony-stimulating factor (Eo-CSF) activity in the pleural fluids of six patients with malignant pleurisy caused by lung cancer or malignant mesothelioma during and after intrapleural administration of IL-2. Results showed that intrapleural administration of IL-2 induced marked eosinophilia in the pleural fluid and moderate eosinophilia in the peripheral blood, and that during IL-2 administration, marked Eo-CSF activity appeared in the pleural fluid before increase in the number of eosinophils, but that this activity did not appear in the peripheral blood. This Eo-CSF activity was inhibited by a combination of anti-IL-5 antibody, anti-IL-3 antibody, and anti-granulocyte/macrophage colony-stimulating factor (anti-GM-CSF) antibody, but not by each antibody alone. Chemotactic activity for eosinophils was also detected in the pleural fluid during IL-2 treatment. These results suggest that eosinophilia in the pleural fluid induced by IL-2 injection into the pleural cavity of patients with malignant pleurisy is due to the Eo-CSF activities of various components, including IL-5, IL-3, and GM-CSF, and chemotactic factors for eosinophils induced locally in the pleural cavity by IL-2.

In plain English

This small clinical and laboratory study at Tokushima University Hospital, Japan, followed six patients with malignant pleurisy (cancer involving the lung lining) whose malignant pleural effusions were being treated. Five had primary lung cancer and one had malignant mesothelioma. Each received 1,000 units of interleukin-2 (IL-2), an immune-signaling protein, injected into the pleural cavity once a day for 14 days. The article does not discuss asbestos. In the pleural fluid, eosinophils (a type of white blood cell) rose from a mean of 13 to 2,718 per cubic millimetre by day 14 of treatment. They fell to 825 two weeks after treatment ended. Mean blood eosinophils rose from 167 to 992 per cubic millimetre by day 14. The pleural fluid showed little eosinophil-growth activity before treatment but high activity on day 14. Combining antibodies against IL-5, IL-3 and GM-CSF blocked this activity completely. Single antibodies did not significantly reduce it in two of three patients tested. Malignant cells disappeared from the fluid during treatment. The authors concluded that several locally produced growth factors and an eosinophil-attracting factor were responsible. They did not identify which cells released these factors.

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 and laboratory study: pleural fluid and blood were measured before, during and after intrapleural IL-2 treatment, with laboratory colony-growth, antibody-blocking and cell-migration tests
• Who was studied: Six inpatients at Tokushima University Hospital, Japan, aged 46 to 73 years, with malignant pleurisy: five with primary lung cancer (adenocarcinoma) and one with malignant mesothelioma. All were studied before conventional anticancer therapy, and IL-2 was given to treat their malignant effusions. Bone marrow from healthy volunteers was used in the laboratory tests.
• Exposure: Recombinant human interleukin-2, given as a 1,000-unit dose into the pleural cavity once a day for 14 days. No asbestos or fiber exposure is studied.
• Main results:
  • In the pleural fluid of all six patients, eosinophils rose from a mean of 13 ± 18 per cubic millimetre before treatment to 2,718 ± 1,296 on day 14 of treatment (n = 6, P < 0.05). Lymphocytes also rose, from 455 ± 255 to 2,291 ± 1,177.
  • Two weeks after treatment ended, pleural fluid eosinophils had decreased significantly, to 825 ± 783 per cubic millimetre. Lymphocytes had not decreased significantly (1,442 ± 874).
  • In the peripheral blood, mean eosinophil counts rose from 167 ± 95 per cubic millimetre before treatment to 992 ± 622 per cubic millimetre on day 14 of treatment (n = 6, P < 0.05). The authors called this moderate eosinophilia.
  • Before treatment, the pleural fluid had little if any eosinophil colony-stimulating (Eo-CSF) activity. It showed high Eo-CSF activity on day 14 of treatment. The patients' blood serum showed no colony-stimulating activity.
  • Pleural fluid from three patients (patients 1, 2 and 5) was tested with antibodies. For patients 1 and 2, single antibodies against IL-5, IL-3 or GM-CSF did not significantly reduce Eo-CSF activity. For patient 5, anti-IL-3 inhibited the activity by 72% and anti-GM-CSF by 67%. Pairs of antibodies inhibited it more than any single antibody, and all three together blocked it completely.
  • IL-2 itself had no eosinophil colony-stimulating activity in the laboratory assay.
  • In three patients, pleural fluid taken on day 14 of treatment attracted about four times as many eosinophils as fluid taken before treatment: 9.4 ± 1.4 versus 2.1 ± 0.9 cells per high-power field (n = 3, P < 0.05).
  • Malignant cells disappeared from the pleural fluid during IL-2 treatment, and no pleural fluid accumulated in any patient after treatment.
• The authors' conclusion: The authors concluded that IL-2 given into the pleural cavity induced eosinophilia in the pleural fluid. They attributed this to several eosinophil colony-stimulating factors, including IL-5, IL-3 and GM-CSF, together with an eosinophil-attracting (chemotactic) factor produced locally.
• Limitations the authors state:
  • The authors did not identify which cells in the pleural cavity released the eosinophil colony-stimulating factor.
  • The authors had no information on whether other cells, such as monocytes and fibroblasts, contributed growth factors.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Cavity, Pleurisy, Lung Cancer, Malignant Mesothelioma, Macrophage.

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