title: Pharmacological Potential of NOX2 Agonists in Inflammatory Conditions.
abstract: CONCLUSIONS
  New insights into the role of reactive oxygen species (ROS) show that activators of the phagocyte NADPH oxidase 2 (NOX2) complex have the potential to be therapeutic in autoimmune and inflammatory conditions. It is, however, essential to elucidate the consequence of targeting the NOX2 complex, as it might lead to different outcomes depending on disease context and specificity, dose, and timing of ROS production.
  
  
  BACKGROUND
  Increasing evidence is suggesting that the role of the NOX2 complex is far more complex than previously anticipated. In addition to the well-described antimicrobial response, ROS also have immune and inflammatory regulatory effects. Compounds increasing NOX2-dependent ROS production have been shown to be effective both in preventing and in treating inflammatory manifestations in animal models of autoimmune diseases. Altogether, these results suggest the possibility of activating the NOX2 complex for the treatment of autoimmune inflammatory diseases while restoring and maintaining a balanced ROS regulation.
  
  
  RESULTS
  The complexity of the NOX system and the derived ROS is important and must be considered when designing the programs for the development of NOX2-activating drugs, as well as for validation of selected hits, to successfully identify substances effective in treating inflammatory and autoimmune conditions. In addition, it is important to consider the complex downstream immunological effects and safety for drugs that increase the production of ROS.
  
  
  CONCLUSIONS
  There is a strong potential for the development of ROS-inducing drugs, targeting the NOX2 complex, which are effective and safe, for the treatment of inflammatory autoimmune disorders. In such drug development, one must carefully investigate the pharmaceutical properties, including both efficacy and safety of the drugs. In addition, the immunological pathways of this new treatment strategy need careful examination.
authors.affiliation: 1 Redoxis AB, Medicon Village , Lund, Sweden .
authors.forename: Malin
authors.initials: M
authors.lastname: Hultqvist
authors.affiliation: 1 Redoxis AB, Medicon Village , Lund, Sweden .
authors.forename: Peter
authors.initials: P
authors.lastname: Olofsson
authors.affiliation: 1 Redoxis AB, Medicon Village , Lund, Sweden .
authors.forename: Fredrik K
authors.initials: FK
authors.lastname: Wallner
authors.affiliation: 2 Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008562:Membrane Glycoproteins / Q000819:agonists / Q000494:pharmacology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases