Editorial Views  |   January 2003
The Alveolar Epithelium: Suspect or Innocent Bystander?
Author Affiliations & Notes
  • Michael A. Gropper, M.D., Ph.D.
  • Jeanine Wiener-Kronish, M.D.
  • *Associate Professor of Anesthesia and Physiology, Director, Critical Care Medicine, Associate Investigator, †Professor of Anesthesia and Medicine, Investigator, Cardiovascular Research Institute, University of California, San Francisco, California.
Article Information
Editorial Views
Editorial Views   |   January 2003
The Alveolar Epithelium: Suspect or Innocent Bystander?
Anesthesiology 1 2003, Vol.98, 3-4. doi:0000542-200301000-00003
Anesthesiology 1 2003, Vol.98, 3-4. doi:0000542-200301000-00003
THE alveolar epithelium is often viewed as a passive bystander in respiratory function, functioning primarily as a barrier. Through the work of Pan et al.  1 and others, 2–4 we have learned that it plays an active role in maintaining homeostasis in the alveolar space through production of key proteins, such as surfactants, surfactant apoproteins, and cytokines, and through the clearance of excess alveolar liquid via  the activity of basolateral sodium–potassium ATPases. These synthetic and homeostatic functions become particularly important in the setting of acute lung injury, in which failure of the alveolar epithelium is associated with increased mortality. 5,6 
Studying the alveolar epithelium is complex;in vivo  studies are complicated by the participation of a number of active cell types, including alveolar type I and type II cells and alveolar macrophages. To determine the contributions of each cell type is impossible. Alternatively, in vitro  studies are complicated by the fact that, thus far, it has proved impossible to culture pure alveolar type I cells, the cell type that provides the majority of cells forming the alveolar barrier. Nevertheless, in vitro  studies have provided crucial information about the metabolic and synthetic activity of the alveolar epithelial barrier.
In this issue of Anesthesiology, Giraud et al.  7 report an elegant series of experiments describing the effects of inhaled anesthetics on the ability of alveolar type II cells to produce inflammatory cytokines. Using recombinant murine interleukin (IL) 1β–primed alveolar type II cells, Giraud et al.  7 showed reversible inhibition of IL-6, macrophage inflammatory protein 2, and monocyte chemoattractant protein 1 secretion using clinically relevant concentrations of inhaled anesthetics. The reduced secretion was not a result of toxicity, as the investigators controlled for cell viability by measuring lactate dehydrogenase release, which was not increased. It is interesting to note that the inhibitory effect was identical in all three anesthetics tested, suggesting a common mechanism. The effect of the anesthetics appeared to be at the transcriptional level, as macrophage inflammatory protein 2 mRNA concentrations were decreased in a similar manner to the protein. It is intriguing to speculate what might have happened to the mRNA concentrations of a “housekeeping” gene such as B-actin, which might have suggested an effect of differential gene expression, perhaps mediated by the transcription factor nuclear factor κΒ, as opposed to global suppression of transcriptional activity caused by the anesthetics.
What are the implications of the findings of Giraud et al.  7 ? First, there is increasing evidence that anesthetics affect alveolar type II cellular function in vitro  8,9 and in animals, 10,11 so they likely have similar effects in humans. The complex interactions between the cellular components of the alveolar space likely are responsible for the diversity of responses seen with common injuries such as pneumonia or aspiration of gastric contents. Could inhaled anesthetics be used as a therapy in most patients with acute lung injury? This seems unlikely, as the same authors have shown that prolonged exposure to anesthetics may induce cytotoxicity. In addition, Molliex et al.  8 demonstrated halothane-induced inhibition of sodium–potassium ATPase activity in alveolar type II cells, which would be expected to worsen or inhibit alveolar liquid clearance in the setting of acute lung injury. Caution should be exercised in assuming that less inflammation in the lung is good: inflammation may be beneficial, as it plays a key role in bacterial killing. Perhaps more interesting is to speculate what effects inhaled anesthetics may have in a patient who suffers an intraoperative infectious insult to the lung, either through the bloodstream (bacteremia) or airspaces (gastric aspiration). Should these patients be transitioned to an intravenous anesthetic in an effort to spare the alveolar epithelium any adverse effects? The answer to this question will require careful in vivo  analysis, but we now have the ability to measure the response of a number of systems simultaneously using modern molecular genetic techniques such as gene chip analysis. Until then, a change in clinical practice is not justified; however, the innovative studies of Giraud et al.  7 suggest that manipulation of the alveolar epithelium may be a strategy that we eventually can employ to decrease the effects of acute lung injury.
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Molliex S, Crestani B, Dureuil B, Bastin J, Rolland C, Aubier M, Desmonts JM: Effects of halothane on surfactant biosynthesis by rat alveolar type II cells in primary culture. A nesthesiology 1994; 81: 668–76Molliex, S Crestani, B Dureuil, B Bastin, J Rolland, C Aubier, M Desmonts, JM
Nishina K, Mikawa K, Morikawa O, Obara H, Mason RJ: The effects of intravenous anesthetics and lidocaine on proliferation of cultured type II pneumocytes and lung fibroblasts. Anesth Analg 2002; 94: 385–8Nishina, K Mikawa, K Morikawa, O Obara, H Mason, RJ
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