To the Editor:
We are pleased that Lex and Uhlig1 come to the same conclusion we published more than 15 yr ago,2 that the role of inflammatory cytokines is minor (if there is indeed any role at all) during ventilator-induced lung injury (VILI). However, we and Dr. Uhlig have had different perspectives on that matter for years. Indeed, in response to an article we wrote on the role of cytokines during VILI,3 Uhlig did not agree with our contention that cytokine secretion by the lungs is a by-product without physiologic significance. In contrast, he emphasized the importance of cytokine mediators in the pathogenesis of VILI.4
We believe that the article by Lex and Uhlig1 and the accompanying editorial5 omitted some key references that illustrate the role of mediators in lung injury in a broader context. For example, cytokines might be important in VILI only in the setting of another source of inflammation,6 and von Bethmann et al.7 demonstrated that inflammatory cytokines and prostanoids may be produced by the lungs during low tidal volume (noninjurious) ventilation. Therefore it is not possible to determine the exact role of cytokines in the development of VILI, because their elevation, when observed, may be either a cause (which we think unlikely) or a consequence of lung overdistension, and the results of experimental studies (including those by Uhlig) are often inconsistent.3 Finally, even if mediators play a role in propagating lung injury, the most important clinical aspect is that simply reducing tidal volume has resulted in a marked reduction in mortality from adult respiratory distress syndrome, whereas to date all clinical trials of antimediator therapies in critically ill patients have been negative.
The authors declare no competing interests.