The Relationship Between Circulating Bone Morphogenetic Protein-4 and Inflammation Cytokines in Patients Undergoing Thoracic Surgery: A Prospective Randomized Study

Background: Bone morphogenetic protein-4 (BMP4) has been identified as an inflammation regulator in the diseases of arteries and other organs. However, the relationship between circulating BMP4 and perioperative inflammation remains unclear. Patients and Methods: Forty patients undergoing lobectomy were randomly allocated into the Control group (not receiving flurbiprofen) and the Flurb group (received 100mg flurbiprofen during surgery). Arterial blood was obtained before surgery (T1), at the end of surgery (T2), and 24 hours after surgery (T3) to test the plasma concentrations of BMP4, its antagonist Noggin, interleukin (IL)-10, tumor necrosis factor-alpha (TNF-alpha), and IL-10. The relationship between BMP4 and other variables and the effects of flurbiprofen on BMP4 changes were investigated. Results: A total of 35 patients were included. Circulating BMP4 was positively correlated with IL-10 (P<0.01, r=0.575) and TNF-alpha (P<0.01, r=0.491), negatively correlated with IL-10 (P<0.01, r=-0.675), but not correlated with Noggin. The plasma concentrations of BMP4, IL-10, and TNF-alpha increased at T2 (P<0.01, compared with T1) and decreased at T3 (P<0.05, compared with T2). BMP4 concentrations at T3 were significantly higher than at T1 in the Control group (P<0.05), while showing no significant difference in the Flurb group. However, in the Flurb group, the relative changes of BMP4 and IL-10 at T2 and T3 were significantly lower than those in the Control group. Conclusion: Circulating BMP4 was elevated during surgery and highly correlated with inflammation cytokines. The elevation of BMP4 and inflammatory cytokines could be alleviated by flurbiprofen, indicating that BMP4 may exert pro-inflammatory properties via cyclooxygenase-II signaling pathways.