Upregulation of Inflammatory Mediators in Lung Cancer and Their Modulation by Oral Anticoagulant Therapy

• Published in: The FASEB journal 2007, Vol.21 (6), p.A768-A768
• Main Authors: Hoppensteadt, Debra, Demir, Muzaffer, Cunanan, Josephine, Iqbal, Omer, Bick, Rodger, Fareed, Jawed
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.A768-d

Although its pathogenesis is not fully understood, venous thromboembolic events (VTE) significantly contribute to the increased mortality in lung cancer patients. Even patients undergoing therapeutic interventions are at high risk to develop VTE. In a prospective, randomized, controlled study, patients with inoperable lung cancer (n=100) were randomized to receive chemotherapy, radiation and warfarin (INR 1.5–2.5) or chemotherapy and radiation alone (n=50). Blood samples were drawn prior to and after the second treatment cycle with warfarin. All samples were analyzed for tumor necrosis factor alpha (TNFα), CD 40 ligand (CD40L), C‐reactive protein (CRP), interleukin 1 beta (IL‐1β), asymmetric dimethylarginine (ADMA) and nitric oxide (NO). Levels of all of the markers of inflammation decreased (13–50%) relative to pre‐treatment values following warfarin treatment. In patients not treated with warfarin, an increase (18–46%) in the levels of TNFα, CD40L and NO was observed. CRP and ADMA levels decreased, but to a lesser extent that in the warfarin‐treated patients. IL‐1β levels were unchanged in the warfarin‐free group. The levels of various inflammatory markers are upregulated in lung cancer suggesting a pathogenic role for this process. Warfarin treatment down‐regulated the inflammatory process. The clinical relevance of these observations require additional investigations with other anticoagulant drugs.