Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Abstract

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an acute respiratory worsening of unidentifiable cause that sometimes develops during the clinical course of IPF. Although the incidence of AE-IPF is not high, prognosis is poor. The pathogenesis of AE-IPF is not well understood; however, evidence suggests that coagulation abnormalities and inflammation are involved. Thrombomodulin is a transmembranous glycoprotein found on the cell surface of vascular endothelial cells. Thrombomodulin combines with thrombin, regulates coagulation/fibrinolysis balance, and has a pivotal role in suppressing excess inflammation through its inhibition of high-mobility group box 1 protein and the complement system. Thus, thrombomodulin might be effective in the treatment of AE-IPF, and we and other groups found that recombinant human soluble thrombomodulin improved survival in patients with AE-IPF. This review summarizes the existing evidence and considers the therapeutic role of thrombomodulin in AE-IPF.

Keywords: HMGB-1; acute exacerbation of IPF; coagulation; inflammation; thrombomodulin.

Figure 1

Coagulation and fibrinolysis cascade. PC: protein C; aPC: activated protein C; FDP: Fibrin degradation products; PAI-1: plasminogen activator inhibitor 1; t-PA: tissue plasminogen activator.

Figure 2

High-mobility group box-1 (HMGB-1) actions in lungs of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). TLRs: toll-like receptors; RAGE: receptors for advanced glycation end products.