Modulation of inflammatory response of wounds by antimicrobial photodynamic therapy

Abstract

Background and aims: Management of infections caused by Pseudomonas aeruginosa is becoming difficult due to the rapid emergence of multi-antibiotic resistant strains. Antimicrobial photodynamic therapy (APDT) has a lot of potential as an alternative approach for inactivation of antibiotic resistant bacteria. In this study we report results of our investigations on the effect of poly-L-lysine conjugate of chlorine p6 (pl-cp6) mediated APDT on the healing of P.aeruginosa infected wounds and the role of Nuclear Factor kappa B (NF-kB) induced inflammatory response in this process. Materials and method: Excisional wounds created in Swiss albino mice were infected with ~10 7 colony forming units of P.aeruginosa. Mice with wounds were divided into three groups: 1) Uninfected, 2) Infected, untreated control (no light, no pl-cp6), 3) Infected, APDT. After 24 h of infection (day 1 post wounding), the wounds were subjected to APDT [pl-cp6 applied topically and exposed to red light (660 ± 25 nm) fluence of ~ 60 J/cm 2 ]. Subsequent to APDT, on day 2 and 5 post wounding (p.w), measurements were made on biochemical parameters of inflammation [toll like receptor-4 (TLR-4), NF-kB, Inteleukin (IL)-[1α, IL-ß, and IL-2)] and cell proliferation [(fibroblast growth factor-2 (FGF-2), alkaline phosphatase (ALP)]. Results: In comparison with untreated control, while expression of TLR-4, NF-kB (p105 and p50), and proinflammatory interleukins (IL-1α, IL-1ß,IL-2) were reduced in the infected wounds subjected to APDT, the levels of FGF-2 and ALP increased, on day 5 p.w. Conclusion:The measurements made on the inflammatory markers and cell proliferation markers suggest that APDT reduces inflammation caused by P.aeruginosa and promotes cell proliferation in wounds.

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

“…All showed that PDT reduced the infection. Specifically, the PDT‐treated infected wounds had significantly ( P < .05) lower bacterial counts at various time points than infected control wounds that had not been treated or had been treated with photosensitiser only or light only …”

“…The animal species used in the 19 studies were mice (n = 16) and rats (n = 3) . Of the 16 mouse studies, nine used BALB/c mice, 4 utilised Swiss albino mice, two used C57BL/ksj db/db mice, and one used CD1 mice . One study did not report the mouse strain that was used.…”

“…It was used in two studies . Other used photosensitisers were 5‐phenyl‐10; 15, 20‐tris (N‐methyl‐4‐pyridyl) porphyrin chloride (PTMPP); sinoporphyrin sodium (also known as DVDMS); indocyanine green (ICG); pentalysine β‐carbonylphthalocyanine zinc (ZnPc‐[Lys] 5 ); zinc phthalocyanine tetrasulfonate (ZnPc‐S 4 ); poly‐L‐lysine conjugate of chlorine p6 (pl‐cp6), β‐lactamase‐activated EtNBS (LAEtNBS); RLP068/Cl, toluidine blue O (TBO); polyethylenimine‐chlorin(e6) (PEI‐ce6); and poly‐ l ‐lysine‐chlorin e6 (pL‐ce6) …”

“…The photosensitisers were administered topically in 13 studies, by subcutaneous injection in one study, and by intraperitoneal injection in another study . In one study, burn wounds were simultaneously treated by both topical application and injection under the wound .…”

“…Seventeen studies measured the effect of PDT on wound bacteria counts or bioluminescence . All showed that PDT reduced the infection.…”