Photodynamic therapy using intra-articular photofrin for murine MRSA arthritis: Biphasic light dose response for neutrophil-mediated antibacterial effect

Masamitsu Tanaka, Manabu Kinoshita, Yasuo Yoshihara, Nariyoshi Shinomiya, Shuhji Seki, Koichi Nemoto, Michael R. Hamblin, Yuji Morimoto

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Background and Objective: Bacterial arthritis does not respond well to antibiotics and moreover multidrug resistance is spreading. We previously tested photodynamic therapy (PDT) mediated by systemic Photofrin® in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) arthritis, but found that neutrophils were killed by PDT and therefore the infection was potentiated. Study Design/Materials and Methods: The present study used an intra-articular injection of Photofrin® and optimized the light dosimetry in order tomaximize bacterial killing and minimize killing of host neutrophils. MRSA (5 × 107 CFU) was injected into the mouse knee followed 3 days later by 1 μg of Photofrin® and 635-nm diode laser illumination with a range of fluences within 5 minutes. Synovial fluid was sampled 6 hours or 1-3, 5, and 7 days after PDT to determine MRSA colony-forming units (CFU), neutrophil numbers, and levels of cytokines. Results: A biphasic light dose response was observed with the greatest reduction of MRSA CFU seen with a fluence of 20 J cm-2, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. Consistent with these results, a significantly higher concentration of macrophage inflammatory protein-2, a CXC chemokine, and greater accumulation of neutrophils were seen in the infected knee joint after PDT with a fluence of 20 J cm-2 compared to fluences of 5 or 70 J cm-2. Conclusion: PDT for murine MRSA arthritis requires appropriate light dosimetry to simultaneously maximize bacterial killing and neutrophil accumulation into the infected site, while too little light does not kill sufficient bacteria and too much light kills neutrophils and damages host tissue as well as bacteria and allows bacteria to grow unimpeded by host defense.

Original languageEnglish
Pages (from-to)221-229
Number of pages9
JournalLasers in Surgery and Medicine
Volume43
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

Keywords

  • Antimicrobial effect
  • Chemokine
  • Macrophage inflammatory protein-2
  • Neutrophil-mediated host defense
  • Photoinactivation

ASJC Scopus subject areas

  • Surgery
  • Dermatology

Fingerprint

Dive into the research topics of 'Photodynamic therapy using intra-articular photofrin for murine MRSA arthritis: Biphasic light dose response for neutrophil-mediated antibacterial effect'. Together they form a unique fingerprint.

Cite this