Ann Thorac Surg 2006;82:478-479
© 2006 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Invited commentary
Thomas K. Varghese, Jr, MD
Section of Thoracic Surgery, University of Michigan, 2120 Taubman Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109
(Email: vargthom{at}umich.edu).
Ischemia–reperfusion lung injury resulting in pulmonary dysfunction is a major source of morbidity and mortality after cardiac surgery and lung transplantation. Transbronchial biopsies performed after lung transplantation demonstrate histologic features of diffuse alveolar damage in more than 30% of patients [1]. This is associated with severe graft dysfunction in about 20% of recipients [2], and is the most common cause of early mortality after lung transplantation [3–5]. Postoperative lung dysfunction after cardiopulmonary bypass is also in part associated with lung ischemia–reperfusion injury [6].
The events after ischemia–reperfusion, although closely related, cause lung injury by activation of different inflammatory pathways [6, 7]. The authors of the present report [8], used a well-established rodent model of lung ischemia–reperfusion injury [9] to analyze the role of interlukin-6 (IL-6). In hemorrhagic and endotoxin-induced shock models, both systemically and locally given IL-6 decreased neutrophil extravasation, inhibited inflammatory cytokines such as tumor necrosis factor-
, decreased tissue permeability, and improved animal survival [10–14].
Signal transducers and activators of transcription (STAT) factors are a family of cytoplasmic transcription factors that mediate intracellular signaling initiated at cytokine cell surface receptors and transmitted to the nucleus. Different STATs are activated by distinct groups of cytokines, with interferon-
activating STAT-1 and IL-6 classically described as activating STAT-3. In the present report, however, IL-6 was found to reduce STAT-3 activation. STAT-1 has been shown to induce apoptosis in cardiac myocytes, whilst STAT-3 is able to protect cardiac myocytes after ischemia–reperfusion [15]. A direct correlation between the degree of apoptosis and pulmonary dysfunction after ischemia–reperfusion remains controversial, however, with the deterioration in lung function correlating to the degree of necrosis and not apoptosis [16].
These are just some examples of the difficulties that have been encountered during the elucidation of molecular events of ischemia–reperfusion and attempting to correlate their clinical importance. The role of exogenous IL-6 in inhibiting NF
B has been studied in one other publication [15], and the present work describes the activation pattern of STAT-3 after lung ischemia–reperfusion injury.
The limitations of current therapies largely arise from our limited understanding of the molecular events that modulate the severity of damage that arises from ischemia–reperfusion injury. Understanding these underlying cellular and molecular signaling events is critical to the development of new therapeutic approaches.
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