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There are several antiproliferative and angiogenic factors, recently have been discovered (IL-27, IL-29, IL-31 and IL-33), but they have not been tested yet in lung cancer patients. The aim of this pilot study was to assess the clinical usefulness of determination of IL-27, IL-29, IL-31 and IL-33 in advanced stages of lung cancer. Patients and Methods: The study included 45 patients (38 males; mean age 62 years; 45 with advanced NSCLC). Serum and BALF cytokine concentrations were evaluated by ELISA method before chemotherapy. The comparative groups consisted of patients with sarcoidosis (BBS, n = 15), hypersensivity pneumonitis (HP, n = 8) and healthy subjects (n = 15). Results: The serum IL-29 levels were higher in NSCLC patients than in the sarcoidosis group. However, serum IL-27, IL-31 and IL-33 did not differ markedly between: NSCLC, BBS, HP and the control group. Concentrations of IL-29 and IL-31 in BALF did not differ significantly between investigated groups. In all groups levels of IL-27 and IL-29 are significantly higher in serum than in BALF. Concentrations of IL-31 in BBS, HP and control groups tended to higher in BALF than in serum. These differences were significantly in NSCLC patients. Patients in stage IIIB of NSCLC had higher serum levels of IL-29 than these in stage IV. Lung cancer patients with partial remission (PR) after chemotherapy had significantly higher concentration of IL-27 in BALF than patients with SD. However, patients with SD had higher levels of IL-29 in BALF than patients with PD. A negative correlation was found between serum IL-31 levels before therapy and time to progression of NSCLC. Conclusion: Determination of IL-27, IL-29 and IL-31 in serum and BALF can be useful in clinical practice, but their practical significance needs further studies.