Clarithromycin Inhibits the Development of Dermatitis in NC/Nga Mice

Abstract

Background: Colonization of Staphylococcus aureus on the skin is one of the exacerbating factors of atopic dermatitis (AD). Reduction of bacterial colonization in these lesions was reported to be effective for the treatment of subjects with AD. Clinical trials have demonstrated the efficacy of FK-506 (an immunosuppressive macrolide) ointment for AD, and many case reports have been published regarding its positive effects for other inflammatory skin diseases. Clarithromycin (CAM) is a macrolide antibiotic with immunological effects. One patient with AD was treated effectively with oral CAM for Helicobacter pylori infection. NC/Nga (NC) mice have recently been recognized to be a model of AD. Methods: We examined the effects of CAM on the development of dermatitis, infiltration of mast cells and MHC class II-positive cells in the skin and the colonization of S. aureus on the skin of NC mice. CAM was compared with cefaclor, an antibiotic with no immunological effects. Results: CAM suppressed the development of dermatitis at 5 and 6 weeks to a statistically significant degree, and these effects gradually weakened, but the severity of the dermis of CAM-treated mice was milder than in control mice. Dexamethasone was effective in the case of development of dermatitis at 5 weeks. These effects gradually weakened, and the difference between dexamethasone-treated mice and control mice disappeared. The severity of the skin lesions in CAM-treated mice was the lowest of the three groups at 9 weeks of observation. Histological analyses revealed that infiltration of inflammatory cells, especially degranulated mast cells and MHC class II-positive cells, was significantly reduced. Thickening of the epidermis and hyperkeratosis in CAM-treated mice were less than in control mice. CAM and cefaclor completely inhibited S. aureus on the skin of NC mice, for all experimental periods. Dexamethasone provided inhibition at 5 weeks, but eventually the difference between dexamethasone-treated mice and control mice disappeared. Conclusions: CAM inhibited the development of dermatitis for the first half of the experimental period in NC mice as a result of antibacterial and immunological effects. Our data show that CAM can be an effective antibiotic for AD with respect to delaying the development of dermatitis.

Topical Azithromycin and Clarithromycin Inhibit Acute and Chronic Skin Inflammation in Sensitized Mice, with Apparent Selectivity for Th2-Mediated Processes in Delayed-Type Hypersensitivity

“…This clear action undoubtedly contributed to the reduction in ear swelling, to which histamine would have made a major contribution and may help to explain why the macrolides inhibited chronic OXA-DTH induced ear swelling, with little effect on leukocyte accumulation. A similar reduction by orally administered clarithromycin (100 mg/kg, three times per week for 9 weeks) of the number of degranulated mast cells in the skin was also observed in NC/Nga mice infected with S. aureus which develop dermatitis, with infiltration of mast cells and MHC class II-positive cells in the skin [23]. It is unclear, though, whether clarithromycin, under these conditions, was acting as an antibacterial or anti-inflammatory agent.…”

“…However, the molecular and cellular mechanisms of inflammation in these animal models remained unexplored. Hashimoto et al [23] studied the possible mechanism of action of oral clarithromycin in Staphylococcus aureus-induced dermatitis in NC mice, but did not distinguish antibacterial from anti-inflammatory effects.…”

Combined Antibacterial and Anti-Inflammatory Activity of a Cationic Disubstituted Dexamethasone-Spermine Conjugate

“…Host inflammatory response to infection can strongly aggravate its consequences, and, in many cases, the current therapy for infection involves antibacterial and anti-inflammatory drug administration. Indeed, combined antibacterial and anti-inflammatory treatment with dexamethasone was found beneficial in some ocular (33,46), airway (44), skin (25), and central nervous system infections (12). Corticosteroids are also used early in CF lung disease to prevent and delay inflammation leading to lung damage and respiratory failure.…”

Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models

“…The suppressive effect of many compounds on dermatitis was therefore evaluated using NC/Nga mice from 7 to 8 weeks of age [36][37][38]. KF66490 inhibited the symptoms of dermatitis in NC/Nga mice.…”