MTBE: not carcinogenic.

I read with interest the EHP supplement on oxygen radicals and lung injury (vol. 102, supplement 10). I would like to take this opportunity to comment about this supplement and raise a key issue concerning the major concepts regarding the mechanisms of cellular injury in inflammatory diseases. As an active investigator in this field of research, I cannot fully understand why there was no mention in the supplement about the basic understanding that cellular damage in inflammation is multifactorial. The nonexpert reader of this supplement might receive an erroneous impression that oxygen radicals, per se, are the exclusive toxic agonists that induce cellular injury. Many in this field share the view that cellular damage in inflammatory diseases might be caused by a "coordinated cross-talk" among oxidants, membrane-damaging agents, proteinases, arachidonic acid metabolites, phospholipases, cationic proteins, and cytokines. All these agents are likely to be present in sites of infection and inflammation. But sadly, none of the publications elaborating on this multifactorial view are quoted in modern textbooks or in symposia on inflammation and inflammatory diseases. Instead, the literature is filled with publications that insist on a single agonist, be it an oxidant, a protease, a cytokine, etc., in experimental models. No attempt to integrate the various agonists into the full picture is made. Several of our publications (1-7) deal with synergistic interactions among multiple proinflammatory agonists in cellular injury during inflammation. I believe that this issue is important, timely, and might contribute to an understanding of how drugs, chemicals, and xenobiotics function in vivo.