1 The concept that
nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of
nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. 2 Since
hydrocortisone is the most widely used anti-inflammatory
drug for the treatment of skin
inflammation, we compared the anti-inflammatory effects of
hydrocortisone to an NO-releasing derivative of
hydrocortisone,
NCX 1022, in a murine model of
irritant contact dermatitis, induced by epidermal application of
benzalkonium chloride. 3 Topical pre- and post-treatment with
NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of
inflammation (from 1 to 5 h).
NCX 1022, but not
hydrocortisone, significantly inhibited granulocyte recruitment (tissue
myeloperoxidase activity). Histological samples of mouse ears treated with
NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to
hydrocortisone-treated tissues. 4 With intravital microscopy, we observed that both pre- and post-treatments with
NCX 1022 were more effective than
hydrocortisone in terms of inhibiting
benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. 5 These results suggest that by releasing NO,
NCX 1022 modulates one of the early events of skin
inflammation: the recruitment of leukocytes to the site of
inflammation. Overall, we have shown that NO-
hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound.