Chest
Volume 110, Issue 2, August 1996, Pages 433-436
Journal home page for Chest

Clinical Investigations: Malignancies
Elevation of Interleukin-10 Levels in Malignant Pleural Effusion

https://doi.org/10.1378/chest.110.2.433Get rights and content

Study objective

Human immunity has been found to have two major components, cellular and humoral immunity. T-helper type 1 (Th1) pathway favors cellular immunity and Th2 pathway favors humoral immunity. Early determination toward Th1 and Th2 cells in the immune response is dependent on the balance between interleukin-12 (IL-12), which favors Th1 responses, and IL-4, which favors Th2 responses. IL-2 and interferon-γ (IFN-γ) are produced in the Th1 pathway, and IL-4 and IL-10 are produced in the Th2 pathway. Lack of cellular immunity, IL-2, and IFN-γ had been reported in malignant pleural effusions. However, to our knowledge, there are no previous reports on other cytokine components involving Th1 or Th2 pathway. The present study was designed to answer these questions.

Design

Cytokine levels in peripheral blood and pleural fluid of 21 patients with malignant pleural effusion, including IL-4, IL-10, and IL-12, were analyzed with enzyme-linked immunosorbent assays. Lymphocyte subpopulations of peripheral blood and pleural effusion were also studied by using flow cytometry.

Measurements and results

The results showed a significant increase in IL-10 level as compared with blood samples. IL-4 and IL-12 were below minimal detectable concentrations both in the blood and the effusion. The ratio of pleural helper T cells was significantly higher than in the blood (p=0.0002). The ratio of pleural natural killer (NK) cells was significantly lower than in the blood (p=0.0001). The ratio of pleural suppressor T cells was lower than blood with borderline significance (p=0.0522). No significant change in B-lymphocyte ratio between blood and pleural effusion was found (p=0.2471). There was no correlation between difference in IL-10 level and lymphocyte subpopulation of pleural effusion and blood samples.

Conclusions

Helper T-cell subpopulations were increased while NK and suppressor T-cell subpopulations were decreased in malignant pleural effusions. The decrease in NK cell subpopulations with elevated IL-10 and minimal IL-12 concentration in neoplastic pleural effusion would suggest the usage of IL-12 or antibody of IL-10 to improve local cellular immunity. Further study is needed.

Section snippets

MATERIALS AND METHODS

Pleural fluid and peripheral blood were simultaneously obtained from 21 patients with newly diagnosed neoplastic pleural effusions. Major clinical characteristics of these 21 patients are summarized in Table 1. All patients had histocytologically proved neoplastic pleural effusion.

Cytokine analysis was performed by using the ELISA method. Peripheral blood samples and pleural effusions were centrifuged at 1,000g for 15 min at 4°C. The supernatant was collected and stored at −70°C in aliquots of

RESULTS

Cytokine analyses of all specimens from the patients revealed that IL-4 and IL-12 were either undetectable or below minimal detectable concentration of the ELISA kits both in the effusions and blood. Most of the patients had detectable IL-10 in their effusion and blood, and the levels in the pleural effusion were significantly higher than in blood (p=0.0001). The cytokine data are shown in Table 1.

The characteristics of the lymphocyte subpopulations in peripheral blood and pleural effusions are

DISCUSSION

In the present study, the percentages of CD3+/CD4+ (helper T cell) lymphocytes were significantly higher in the pleural fluid than in the peripheral blood of patients suffering from malignant pleural effusions. The same data have been reported in neoplastic and tuberculosis pleural effusions previously.14, 15, 16, 17, 18 The finding that a decrease in pleural CD3+/CD8+ (suppressor T cell) lymphocytes in neoplastic pleural effusion has not been reported before (to our knowledge). Because most of

References (22)

  • AntonyVB et al.

    Pleural cell biology in health and disease

    Am Rev Respir Dis

    (1992)
  • Cited by (60)

    • PD-L1 Expression of Tumor Cells, Macrophages, and Immune Cells in Non–Small Cell Lung Cancer Patients with Malignant Pleural Effusion

      2018, Journal of Thoracic Oncology
      Citation Excerpt :

      Malignant pleural effusion is a common complication of lung cancer. Chen et al. reported that tumor-induced immunosuppression could be observed in pleural effusion.4 However, PD-L1 expression in pleural effusion cells has not been reported.

    • Immune checkpoint inhibitors for nonsmall cell lung cancer treatment

      2017, Journal of the Chinese Medical Association
      Citation Excerpt :

      Although the immune system plays an important role in recognizing, controlling, and eradicating cancer, cancer induces immunosuppression through several mechanisms that may suppress effective antitumor immunity, including but not limited to: (1) secretion of immunosuppressive cytokines; (2) loss of major histocompatibility complex antigen expression; (3) and programmed cell death protein 1/programmed cell death protein 1 ligand (PD-1/PD-L1) interaction of tumor cells with immune cells.2–6 In the past, immunotherapy has had minimal success in lung cancer treatment, which was attributed in part to the belief that lung cancer is nonimmunogenic.7–11 Most patients present with advanced disease and are immunosuppressed, as documented by decreased lymphocyte counts and cytotoxic function seen in this patient population.8,11–13

    View all citing articles on Scopus
    View full text