Influence of Intra‐articular Neutrophils on the Effects of Photodynamic Therapy for Murine MRSA Arthritis

Abstract

Although there have been some reports about the cytotoxic effects of photodynamic therapy (PDT) on multidrug-resistant bacteria, there have been few reports in which favorable results of PDT on a local infection site are described. This study aimed to verify the hypothesis that the low efficacy of PDT on a local infection site is due to the cytotoxic effect of PDT on leukocytes. PDT using Photofrin exerted significant cytotoxicity for cultured methicillin-resistant Staphylococcus aureus (MRSA). Nevertheless, this therapeutic modality was not effective for a murine MRSA arthritis model. Approximately 30% of intra-articular leukocytes, mainly neutrophils, died immediately after PDT, and a further decrease in the number of intra-articular leukocytes and atrophy of the synovial tissue were seen 24 h after PDT. Isolated peripheral neutrophils showed significant affinity for Photofrin and showed significant morphological damage, resulting in cell death, when they were subject to PDT using Photofrin. These results indicate that intra-articular neutrophils have an influence on the effects of PDT for MRSA arthritis.

Photodynamic Therapy Using Systemic Administration of 5-Aminolevulinic Acid and a 410-nm Wavelength Light-Emitting Diode for Methicillin-Resistant Staphylococcus aureus-Infected Ulcers in Mice

“…Although wound healing can occur when the bacterial count in granulation tissue is <10 5 CFU/g [34], the bacterial count was not reduced to such a level in the present study. PDT has been reported to exert an immunostimulatory effect [31], [35], [36] and to promote the accumulation of neutrophils, preventing infection [37],[38]. Clinically, topical ALA-PDT has been employed for the photorejuvenation of facial skin by stimulating cellular differentiation and proliferation [39].…”

Photodynamic Therapy Can Induce a Protective Innate Immune Response against Murine Bacterial Arthritis via Neutrophil Accumulation

“…We have investigated the therapeutic effect of PDT for a murine MRSA arthritis model focusing on the role of local host defense mechanisms in the PDT response [33]–[35]. We recently demonstrated that PDT using Photofrin could damage neutrophils as well as bacteria in vitro [33], and in vivo PDT using Photofrin for murine MRSA-induced arthritis showed a pronounced biphasic light dose response [34].…”

“…We recently demonstrated that PDT using Photofrin could damage neutrophils as well as bacteria in vitro [33], and in vivo PDT using Photofrin for murine MRSA-induced arthritis showed a pronounced biphasic light dose response [34]. Light doses that were too low and also light doses that were too high were ineffective and there was an optimum fluence to give the best antibacterial effect.…”

“…Prior to those examinations, we tried to resolve several problems encountered in the previous study [33], [34]. The problems were as follows: firstly, the number of remaining viable MRSA in the joint was decreased once the synovial fluid was collected, therefore the time course of the severity of the infection could not be precisely evaluated with the method of direct counting of colony-forming units (CFU) of the MRSA in the synovial fluid collected from the knee joint; secondly, even the control infections tended to resolve, therefore the PDT effect could not be clearly demonstrated.…”

Can surgical site infections be treated by photodynamic therapy?

“…A recent paper does shed some light on this question. Tanaka et al [11] used a rat model of bacterial arthritis caused by injecting 10 6 CFU of methicillin resistant S. aureus ( MRSA) into the knee joint. They then administered Photofrin systemically by IP injection (regardless of the considerations outlined above) and illuminated the knee joint after 24 h. They found that the PDT treatment actually caused the number of bacteria to increase rather than decrease and they attributed this unfortunate finding to the PDT-mediated killing of neutrophils that could therefore no longer control the infection by phagocytosing the bacteria.…”