PMID- 37121695 OWN - NLM STAT- MEDLINE DCOM- 20230502 LR - 20230502 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 46 IP - 5 DP - 2023 TI - Combination Therapy with Betamethasone and Josamycin Demonstrates Superior Therapeutic Efficacy in an NC/Nga Mouse Model of Atopic Dermatitis. PG - 693-699 LID - 10.1248/bpb.b22-00781 [doi] AB - We have previously demonstrated the excellent bactericidal activity of josamycin against Staphylococcus aureus isolated from patients with atopic dermatitis (AD), with therapeutic efficacy equal to that of betamethasone. The present study was designed to evaluate the effectiveness of combination therapy with betamethasone and josamycin for AD. Betametasone (0.1%) and josamycin (0.1%) were topically administered to NC/Nga mice with severe AD-like skin lesions. Skin severity scores, histological changes in skin lesions, and serum immunoglobulin E (IgE) levels were assessed as indicators of therapeutic efficacy. Topical treatment with both drugs suppressed the skin severity score to a greater degree than betamethasone alone. This was associated with a reduction of epidermal thickening, a reduced density of dermal cellular infiltration, a decreased mast cell count in the dermis, and a reduced serum IgE level. In addition, both drugs in combination markedly reduced the expression of interferon (IFN)-gamma and interleukin (IL)-4 in auricular lymph node cells, as well as the S. aureus count on the lesioned skin. These results show that simultaneous topical application of both drugs can ameliorate severe AD-like skin lesions in NC/Nga mice. It is suggested that combination therapy with betamethasone and josamycin would be beneficial for control of severe AD lesions colonized by S. aureus by inhibiting the development of both T helper (Th) type 1 (Th1) and Th2 cells and also through elimination of superficially located S. aureus. FAU - Matsui, Katsuhiko AU - Matsui K AD - Department of Clinical Immunology, Meiji Pharmaceutical University. FAU - Muranaka, Madoka AU - Muranaka M AD - Department of Clinical Immunology, Meiji Pharmaceutical University. FAU - Yamaguchi, Tomoka AU - Yamaguchi T AD - Department of Clinical Immunology, Meiji Pharmaceutical University. FAU - Maeda, Manami AU - Maeda M AD - Department of Clinical Immunology, Meiji Pharmaceutical University. LA - eng PT - Journal Article PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - HV13HFS217 (Josamycin) RN - 9842X06Q6M (Betamethasone) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Mice MH - Animals MH - *Dermatitis, Atopic/drug therapy/pathology MH - Josamycin/therapeutic use MH - Betamethasone/therapeutic use MH - Staphylococcus aureus MH - Skin/pathology MH - Disease Models, Animal MH - Immunoglobulin E OTO - NOTNLM OT - Staphylococcus aureus OT - atopic dermatitis OT - betamethasone OT - josamycin EDAT- 2023/05/01 00:42 MHDA- 2023/05/02 06:42 CRDT- 2023/04/30 21:23 PHST- 2023/05/02 06:42 [medline] PHST- 2023/05/01 00:42 [pubmed] PHST- 2023/04/30 21:23 [entrez] AID - 10.1248/bpb.b22-00781 [doi] PST - ppublish SO - Biol Pharm Bull. 2023;46(5):693-699. doi: 10.1248/bpb.b22-00781.