Hatfield Stephen, Belikoff Bryan, Lukashev Dmitriy, Sitkovsky Michail, Ohta Akio
New England Inflammation and Tissue Protection Institute, Northeastern University, Boston, Massachusetts 02115, USA.
J Leukoc Biol. 2009 Sep;86(3):545-8. doi: 10.1189/jlb.0908577. Epub 2009 Jun 29.
Here, we attract attention to the possibility of iatrogenic exacerbation of immune-mediated tissue damage as a result of the unintended weakening of the tissue-protecting, hypoxia-adenosinergic pathway. These immunosuppressive, anti-inflammatory pathways play a critical and nonredundant role in the protection of normal tissues from collateral damage during an inflammatory response. We believe that it is the tissue hypoxia associated with inflammatory damage that leads to local inhibition of overactive immune cells by activating A2AR and A2BR and stabilizing HIF-1alpha. We show in an animal model of acute lung injury that oxygenation (i.e., inspiring supplemental oxygen) reverses tissue hypoxia and exacerbates ongoing inflammatory lung tissue damage. However, little has been done to carefully investigate and prevent this in a clinical setting. Similarly, the consumption of caffeine antagonizes A2ARs, resulting in exacerbation of ongoing acute inflammation. It is suggested that although the elimination of hypoxia-adenosinergic immunosuppression is desirable to improve vaccines, it is important to take into account the unintentional effects of supplemental oxygen and caffeine, which may increase collateral, inflammatory tissue damage.
在此，我们提请注意医源性加剧免疫介导的组织损伤的可能性，这是由于组织保护的缺氧 - 腺苷能途径意外减弱所致。这些免疫抑制、抗炎途径在炎症反应期间保护正常组织免受附带损伤方面发挥着关键且不可替代的作用。我们认为，正是与炎症损伤相关的组织缺氧通过激活A2AR和A2BR并稳定HIF-1α，导致过度活跃的免疫细胞受到局部抑制。我们在急性肺损伤动物模型中表明，氧合（即吸入补充氧气）可逆转组织缺氧并加剧正在进行的炎症性肺组织损伤。然而，在临床环境中，对此进行仔细研究和预防的工作做得很少。同样，咖啡因的摄入会拮抗A2AR，导致正在进行的急性炎症加剧。有人认为，虽然消除缺氧 - 腺苷能免疫抑制对于改进疫苗是可取的，但重要的是要考虑补充氧气和咖啡因的意外影响，它们可能会增加附带的炎症性组织损伤。
