The increase in serum soluble ST2 protein upon acute exacerbation of idiopathic pulmonary fibrosis

Background: The human ST2 gene can be specifically induced by growth stimulation in fibroblastic cells, and the soluble ST2 protein (ST2) is expressed preferentially in T-helper type 2 (M) cells. Furthermore, ST2 is induced by proinflammatory stimuli such as tumor necrosis factor-alpha and interleukin-1beta. It has been reported that the inflammatory response in idiopathic pulmonary fibrosis (IPF) is thought to be associated with proinflammatory cytokines and Th2 immune response. Study objective: The objective of this study was to evaluate the relevance of the serum ST2 levels in the pathogenesis of IPF. Design: Retrospective study. Setting: Inpatients in a college hospital. Participants: Forty-nine patients with IPF admitted to our hospital 64 times: 36 patients were admitted once, 11 patients were admitted twice, and 2 patients were admitted three times. The participants also included 200 healthy control volunteers. Measurements and results: Among 64 events in 49 patients with IPF, 50 of the events occurred in a stable state, and 14 events occurred during acute exacerbation. An acute exacerbation of IPF was defined as an accelerated phase of IPF. The serum ST2 levels were measured by enzyme-linked immunosorbent assay. The serum levels of ST2 in the stable state group did not differ from those in the healthy control group, while the serum levels of ST2 in the acute exacerbation group were significantly higher than those in the stable state group or the healthy control group (p < 0.001, acute exacerbation group vs stable state group or healthy control group; acute exacerbation group, 2.76 +/- 0.56 ng/mL; stable state group, 0.44 +/- 0.07 ng/mL; healthy control group, 0.42 +/- 0.03 ng/mL). Furthermore, serum ST2 statistically correlated with lactate dehydrogenase (r = 0.344, p = 0.005) and C-reactive protein (r = 0.496, p < 0.001), and inversely correlated with Pao(2), (r = -0.356, p = 0.018) and the percentage of predicted vital capacity (r = -0.346, p = 0.026). Conclusions: These results suggest that ST2 protein may increase in the serum, reflecting severity in the inflammatory process and Th2 immune response in the IPF lung.