Chest
Volume 117, Issue 2, February 2000, Pages 365-373
Journal home page for Chest

Clinical Investigations
Serum Interleukin-10 Levels as a Prognostic Factor in Advanced Non-small Cell Lung Cancer Patients

https://doi.org/10.1378/chest.117.2.365Get rights and content

Study objective

To investigate the prognostic significance of interleukin (IL)-10 serum levels in advanced non-small cell lung cancer (NSCLC) patients.

Design

IL-10 serum levels were measured before chemotherapy, on completion of therapy, and at follow-up by means of a commercially available enzyme-linked immunoassay. The results were then analyzed in comparison with other prognostic variables, and a model predicting overall survival (OS) and time to treatment failure (TTF) was finally generated.

Setting

University hospital.

Patients

Sixty consecutive patients with TNM stage III or IV NSCLC undergoing conventional platinum-based regimens.

Results

Elevated levels of serum IL-10 were found in cancer patients with respect to healthy control subjects (17.7 ± 4.4 vs 9.2 ± 1.5 pg/mL, respectively; p < 0.05), with patients with metastatic disease showing significantly higher levels than patients with undisseminated cancer (21.0 ± 4.2 vs 14.3 ± 1.2 pg/mL, respectively; p < 0.05). Following completion of treatment, patients were classified as responders if they had achieved either one of the following: complete response, partial response, or stable disease; and nonresponders, in case of progressive disease. Retrospective analysis of basal IL-10 serum levels in these two subgroups showed a significant difference between responders and nonresponders (15.2 ± 2.2 vs 21.4 ± 4.2 pg/mL, respectively; p < 0.05). Moreover, a further significant increase in IL-10 serum levels was observed in nonresponders at the end of therapy (21.4 ± 4.2 vs 26.0 ± 4.3 pg/mL, prechemotherapy and postchemotherapy, respectively; p < 0.05), whereas values in responders were found to have significantly decreased (15.2 ± 2.2 vs 14.8 ± 2.2 pg/mL, prechemotherapy and postchemotherapy, respectively; p < 0.05). Using univariate and multivariate analyses, both OS and TTF were shown to be affected by the mean pathologic levels of IL-10. Stepwise regression analysis identified IL-10 serum level and stage as the prognostic factors related to OS, and IL-10 serum level and performance status as the prognostic factors related to TTF.

Conclusions

In conclusion, this study shows that the measurement of pretreatment IL-10 serum levels is of independent prognostic utility in patients with NSCLC and may be useful for detection of disease progression.

Section snippets

Patients

The study population consisted of 60 consecutive patients with advanced histologically proven and previously untreated NSCLC. All patients had a history of smoking, and none of them was affected by autoimmune diseases, inflammatory bowel disease, chronic liver disease, asthma, allergies, or other concomitant diseases capable of interfering with IL-10 assay. Staging was expressed according to TNM classification on evaluation of findings of physical examination, routine laboratory tests, and

IL-10 Serum Levels

IL-10 serum levels were significantly higher in cancer patients prior to chemotherapy (17.7 ± 4.4 pg/mL; range, 12 to 35 pg/mL; median, 16.3 pg/mL; 95% CI, 15.0 to 19.5; IQR, 6) with respect to control subjects (9.2 ± 1.5 pg/mL; range 7.4 to 12.0; median 9.0; 95% CI, 8.4 to 10.0; IQR, 1.86; p < 0.05). In addition, IL-10 serum levels were shown to be significantly increased in stage IV patients (n = 32; 21.0 ± 4.2 pg/mL; range, 14 to 35; median, 20.0; 95% CI, 19.5 to 22.5; IQR, 4.1) as compared

Discussion

NSCLC is characterized by an aggressive clinical course and poor response to immunotherapy,24, 25 probably because of the ability of NSCLC cells to produce a wide variety of immunosuppressive factors that may allow escape from immune recognition. A candidate for such a factor in humans is IL-10, a pleiotropic type 2 cytokine with suppressive activity against various aspects of the cellular immunity, namely, inhibition of proinflammatory cytokine production, reduction of antigen-specific

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