Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Photochem Photobiol. 2013 May-Jun;89(3):679-82. doi: 10.1111/php.12040. Epub 2013 Feb 19.
We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In this study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB-PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real-time noninvasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, whereas LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P < 0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT.
我们之前报道过，通过关节内注射亚甲蓝（MB）进行光动力疗法（PDT），可以治疗发光型耐甲氧西林金黄色葡萄球菌（MRSA）诱导的关节炎，无论是在治疗模式还是预防模式下都有效。PDT 通过激活趋化因子（如炎症细胞因子或趋化因子）将中性粒细胞募集到小鼠膝关节中。在这项研究中，我们想知道 PDT 联合用于治疗 MRSA 的抗生素是否可以提供额外的益处来控制感染。我们比较了单独使用 MB-PDT、单独使用利奈唑胺（LZD）或万古霉素（VCM）、或 PDT 联合 LZD 或 VCM 的治疗效果。我们使用实时非侵入性成像技术连续监测感染的进展。单独使用 PDT 效果最显著，而单独使用 LZD 无效，单独使用 VCM 则有一定效果。令人惊讶的是，加入 LZD 或 VCM 会降低单独使用 PDT 的疗效（P < 0.05）。鉴于在这种小鼠模型中，PDT 通过刺激中性粒细胞发挥抗菌作用，而不是主动杀死细菌，我们提出 LZD 和 VCM 可能抑制炎症细胞因子的激活而不根除细菌，从而降低 PDT 的疗效。
