Nitrite/ nitrate and cytokine levels in bronchoalvelar lavage fluid of lung cancer patients

Abstract

Cytokines are produced by tumor cells in vitro, but evidence for in vivo increased production of cytokines in cancer patients is controversial. Conversely, nitric oxide (NO) is implicated increasingly in the mediation of cytokine effects. Lung cancer patients may show an increased local production of cytokines and NO, and chronic paracrine exposure of epithelial lung cells to these medicators may influence the production of surfactant phosphatidylcholine. The presence of the cytokine tumor necrosis factor (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6), as well as NO, cyclic guanosine 3'5' monophosphate (cGMP) and phosphatidylcholine levels in bronchoalveolar lavage fluid (BLF) of lung cancer patients were investigated. Bronchoalveolar lavage fluid was obtained from 30 male smokers: 22 patients with squamous cell lung cancer and 8 subjects without cancer. When compared with the control subjects, the cancer patients had elevated BLF levels of TNF alpha (1.58 +/- 0.47 vs. 0.04 +/- 0.02 pg/microgram protein, P < 0.001), IL-6 (1.39 +/- 0.29 vs. 0.04 +/- 0.02 pg/microgram protein, P < 0.001), and NO2-/NO3- (23.3 +/- 5.6 vs 1.1 +/- 0.6 nmol/mg protein, P < 0.001). However, phosphatidylcholine levels were lower in those with cancer than in the control subjects (3.0 +/- 1.2 vs. 24.8 +/- 6.4 micrograms protein, P < 0.001). The results showed in vivo production of inflammatory cytokines in human lung cancer and increased tumor-associated NO production, as suggested by increased levels of nitrite/nitrate in the BLF. A decreased phosphatidylcholine content in the BLF also was found in patients with lung cancer.