Tohoku J. Exp. Med., 2015 April, 235(4)

Tissue Inhibitor of Metalloproteinase-1 Is Responsible for Residual Pleural Thickening in Pleural Tuberculosis

KI-EUN HWANG,¹ YOUNG-JUN SHON,² BYONG-KI CHA,³ MI-JEONG PARK,¹ MIN-SU CHU,¹ YOUNG-JUN KIM,¹ EUN-TAIK JEONG¹ and HAK-RYUL KIM¹

¹Department of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea
²Department of Radiology, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea
³Thoracic & Cardiovascular Surgery, Chonbuk National University Hospital, Jeonju, Jeonbuk, Korea

Residual pleural thickening (RPT) is the most frequent complication associated with pleural tuberculosis, and may occur even after successful anti-tuberculosis medications. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases capable of degrading all components of the extracellular matrix. The proteolytic action of MMPs may be involved in the pathogenesis of tuberculosis. MMP-9, secreted by monocytes and lymphocyte, may lead to long-term fibrosis. The aim of the present study was to determine whether MMP-2 and/or MMP-9 and their specific inhibitors, tissue inhibitors of metalloproteinase 1 (TIMP-1) and TIMP-2, could be used to predict RPT. This retrospective study enrolled 52 patients diagnosed with pleural tuberculosis. Levels of MMP-2, MMP-9, TIMP-1, and TIM-2 were determined in the pleural fluid by ELISA. The RPT was measured on chest X-ray at the completion of treatment and the final follow-up. The average periods of anti-tuberculosis medication and the follow-up after completion of treatment were 6.7 and 7.6 months, respectively. MMP-2 or MMP-9 levels had no significant correlation to RPT. The patients with RPT > 2 mm at the completion of anti-tuberculosis medication and the final follow-up had higher TIMP-1 levels (p = 0.00 and p = 0.001, respectively). However, patients with RPT > 2 mm at the completion of anti-tuberculosis medication had lower TIMP-2 levels (p = 0.005). In a logistic regression model, elevated TIMP-1 levels at the completion of anti-tuberculosis medications were associated with RPT. In conclusion, higher TIMP-1 levels are responsible for the development of RPT and may be helpful for predicting RPT in pleural tuberculosis.

keywords —— matrix metalloproteinase; pleural fluid; pleural tuberculosis; residual pleural thickening; tissue inhibitors of metalloproteinase

© 2015 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2015, 235, 327-333

Correspondence: Hak-Ryul Kim, Department of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine, 344-2 Shinyong-dong, Iksan, Jeonbuk 570-749, Korea.

e-mail: kshryj@wonkwang.ac.kr