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Cell Biochemistry and Biophysics

, Volume 70, Issue 1, pp 539–547 | Cite as

Negative-Pressure Wound Therapy Enhances Local Inflammatory Responses in Acute Infected Soft-Tissue Wound

  • Daohong Liu
  • Lihai Zhang
  • Tongtong Li
  • Guoqi Wang
  • Hailong Du
  • Hongping Hou
  • Li HanEmail author
  • Peifu TangEmail author
Original Paper

Abstract

Clinical studies found that negative-pressure wound therapy (NPWT) displayed significant clinical benefits in the healing of infected wounds. However, the effect of NPWT on local inflammatory responses in acute infected soft-tissue wound has not been investigated thoroughly. The purpose of this study was to test the impact of NPWT on local expression of proinflammatory cytokines, amount of neutrophils, and bacterial bioburden in wound from acute infected soft-tissue wounds. Full-thickness wounds were created on the back of rabbits, and were inoculated with Staphylococcus aureus strain ATCC29213. The wounds were treated with sterile saline-moistened gauze dressings and NPWT with continuous negative pressure (−125 mmHg). Wound samples were harvested on days 0 (6 h after bacterial inoculation), 2, 4, 6, and 8 at the center of wound beds before irrigation for real-time PCR analysis of gene expression of IL-1β, IL-8, and TNF-α. Wound biopsies were examined histologically for neutrophil quantification in different layers of tissue. Quantitative bacterial cultures at the same time point were analyzed for bacterial clearance. Application of NPWT to acute infected wounds in rabbits was compared with treatment with sterile saline-moistened gauze, over an 8-day period. NPWT-treated wounds exhibited earlier and greater peaking of IL-1β and IL-8 expression and decrease in TNF-α expression over the early 4 days (P < 0.05). Furthermore, histologic examination revealed that significantly increased neutrophil count was observed in the shallow layer in wound biopsies of NPWT treatment at day 2 (P < 0.001). In addition, there was a statistically significant decrease of bacteria load from baseline (day 0) at days 2 and 8 in NPWT group (P < 0.05). In conclusion, this study demonstrates that NPWT of acute infected soft-tissue wounds leads to increased local IL-1β and IL-8 expression in early phase of inflammation, which may trigger accumulation of neutrophils and thus accelerate bacterial clearance. Meanwhile, the success of NPWT in the treatment of acute wounds can attenuate the expression of TNF-α, and the result may partly explain how NPWT can avoid significantly impairing wound healing.

Keywords

Infection Negative-pressure wound therapy Inflammatory Cytokine 

Notes

Conflict of interest

We declare that we have no financial and personal relationships with other people or organisations that can inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in this article.

References

  1. 1.
    Fleischmann, W., Strecker, W., Bombelli, M., & Kinzl, L. (1993). Vacuum sealing as treatment of soft tissue damage in open fractures. Der Unfallchirurg, 96, 488–492.PubMedGoogle Scholar
  2. 2.
    Morykwas, M. J., & Argenta, L. C. (1997). Nonsurgical modalities to enhance healing and care of soft tissue wounds. Journal of the Southern Orthopaedic Association, 6, 279–288.PubMedGoogle Scholar
  3. 3.
    Mooney, J. F, 3rd, Argenta, L. C., Marks, M. W., Morykwas, M. J., & DeFranzo, A. J. (2000). Treatment of soft tissue defects in pediatric patients using the VAC system. Clinical Orthopaedics and Related Research, 376, 26–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Song, D. H., Wu, L. C., Lohman, R. F., Gottlieb, L. J., & Franczyk, M. (2003). Vacuum assisted closure for the treatment of sternal wounds: The bridge between debridement and definitive closure. Plastic and Reconstructive Surgery, 111, 92–97.PubMedCrossRefGoogle Scholar
  5. 5.
    Clare, M. P., Fitzgibbons, T. C., McMullen, S. T., Stice, R. C., Hayes, D. F., & Henkel, L. (2002). Experience with the vacuum assisted closure negative pressure technique in the treatment of non-healing diabetic and dysvascular wounds. Foot and Ankle International, 23, 896–901.PubMedGoogle Scholar
  6. 6.
    DeFranzo, A. J., Argenta, L. C., Marks, M. W., Molnar, J. A., David, L. R., Webb, L. X., et al. (2001). The use of vacuum-assisted closure therapy for the treatment of lower-extremity wounds with exposed bone. Plastic and Reconstructive Surgery, 108, 1184–1191.PubMedCrossRefGoogle Scholar
  7. 7.
    Liu, D. S., Sofiadellis, F., Ashton, M., MacGill, K., & Webb, A. (2012). Early soft tissue coverage and negative pressure wound therapy optimises patient outcomes in lower limb trauma. Injury., 43(6), 772–778.PubMedCrossRefGoogle Scholar
  8. 8.
    Fleischmann, W., Lang, E., & Russ, M. (1997). Treatment of infection by vacuum sealing. Der Unfallchirurg, 100, 301–304.PubMedCrossRefGoogle Scholar
  9. 9.
    Morykwas, M. J., & Argenta, L. C. (1997). Nonsurgical modalities to enhance healing and care of soft tissue wounds. Journal of the Southern Orthopaedic Association, 6, 279–288.PubMedGoogle Scholar
  10. 10.
    Pinocy, J., Albes, J. M., Wicke, C., Ruck, P., & Ziemer, G. (2003). Treatment of periprosthetic soft tissue infection of the groin following vascular surgical procedures by means of a polyvinyl alcohol–vacuum sponge system. Wound Repair and Regeneration, 11, 104–109.PubMedCrossRefGoogle Scholar
  11. 11.
    Fleck, T. M., Fleck, M., Moidl, R., Czerny, M., Koller, R., Giovanoli, P., et al. (2002). The vacuum-assisted closure system for the treatment of deep sternal wound infections after cardiac surgery. Annals of Thoracic Surgery, 74, 1596–1600.PubMedCrossRefGoogle Scholar
  12. 12.
    Blum, M. L., Esser, M., Richardson, M., Paul, E., & Rosenfeldt, F. L. (2012). Negative pressure wound therapy reduces deep infection rate in open tibial fractures. Journal of Orthopaedic Trauma, 26, 499–505.PubMedCrossRefGoogle Scholar
  13. 13.
    Peck, M. A., Clouse, W. D., Cox, M. W., et al. (2007). The complete management of extremity vascular injury in a local population: A wartime report from the 332nd Expeditionary Medical Group/Air Force Theater Hospital, Balad Air Base, Iraq. Journal of Vascular Surgery, 45, 1197–1204.PubMedCrossRefGoogle Scholar
  14. 14.
    Orgill, D. P., Manders, E. K., Sumpio, B. E., Lee, R. C., Attinger, C. E., Gurtner, G. C., et al. (2009). The mechanisms of action of vacuum assisted closure: More to learn. Surgery, 146, 40–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Dularay, B., Elson, C. J., Clements-Jewery, S., Damais, C., & Lando, D. (1990). Recombinant human interleukin-1 beta primes human polymorphonuclear leukocytes for stimulus-induced myeloperoxidase release. Journal of Leukocyte Biology, 47, 158–163.PubMedGoogle Scholar
  16. 16.
    Schultz, G. (1994). Molecular regulation of the wound environment. In R. A. Bryant (Ed.), Acute and Chronic Wounds (2nd ed., pp. 413–429). St. Louis: Mosby.Google Scholar
  17. 17.
    Endlich, B., Armstrong, D., Brodsky, J., Novotny, M., & Hamilton, T. A. (2002). Distinct temporal patterns of macrophage-inflammatory protein-2 and KC chemokine gene expression in surgical injury. The Journal of Immunology, 168, 3586–3594.PubMedCrossRefGoogle Scholar
  18. 18.
    Bennett D, Komorowska-Timek E, Gabriel A, et al. (2002). Characterizing the changing gene statement of chronic wounds treated with subatmospheric pressure therapy. Presented at the Plastic Surgery Research Council Annual Meeting.Google Scholar
  19. 19.
    Labler, L., Rancan, M., Mica, L., Härter, L., Mihic-Probst, D., & Keel, M. (2009). Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds. Journal of Trauma-Injury, Infection, and Critical Care, 66(3), 749–757.CrossRefGoogle Scholar
  20. 20.
    Morykwas, M. J., Argenta, L. C., Shelton-Brown, E. I., & McGuirt, W. (1997). Vacuum-assisted closure: A new method for wound control and treatment: Animal studies and basic foundation. Annals of Plastic Surgery, 38(6), 553–562.PubMedCrossRefGoogle Scholar
  21. 21.
    Bassetto, F., Lancerotto, L., Salmaso, R., Pandis, L., Pajardi, G., Schiavon, M., et al. (2012). Histological evolution of chronic wounds under negative pressure therapy. Journal of Plastic, Reconstructive & Aesthetic Surgery, 65(1), 91–99.CrossRefGoogle Scholar
  22. 22.
    Bowler, P. G. (2003). The 10(5) bacterial growth guideline: Reassessing its clinical relevance in wound healing. Ostomy Wound Management, 49(1), 44–53.Google Scholar
  23. 23.
    Trotter, A., Muck, K., Grill, H. J., Schirmer, U., Hannekum, A., & Lang, D. (2001). Gender-related plasma levels of progesterone, interleukin-8 and interleukin-10 during and after cardiopulmonary bypass in infants and children. Critical Care, 5, 343–348.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Kupper, T. S., & Fuhlbrigge, R. C. (2004). Immune surveillance in the skin: Mechanisms and clinical consequences. Nature Reviews Immunology, 4, 211–222.PubMedCrossRefGoogle Scholar
  25. 25.
    Miller, L. S., Pietras, E. M., Uricchio, L. H., Hirano, K., Rao, S., Lin, H., et al. (2007). Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo. The Journal of Immunology, 179(10), 6933–6942.PubMedCrossRefGoogle Scholar
  26. 26.
    Matsukawa, A., Yoshimura, T., Miyamoto, K., Ohkawara, S., & Yoshinaga, M. (1997). Analysis of the inflammatory cytokine network among TNF α, IL-1β, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis. Laboratory Investigation, 76, 629–638.PubMedGoogle Scholar
  27. 27.
    Matsukawa, A., Yoshimura, T., Maeda, T., Ohkawara, S., Takagi, K., & Yoshinaga, M. (1995). Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. The Journal of Immunology, 154, 5418–5425.PubMedGoogle Scholar
  28. 28.
    Johnson, R. J. (1996). Immunology and the complement system. In B. D. Ratner, A. S. Hoffman, F. J. Schoen, & J. E. Lemons (Eds.), Biomaterials science. An introduction to materials in medicine (pp. 173–188). San Diego: Academic Press.Google Scholar
  29. 29.
    Fitzgerald, K. A., O’Neill, L. A. J., Gearing, A. J. H., & Callard, R. E. (2001). The cytokine facts book (2nd ed., pp. 80–84). San Diego: Academic Press.CrossRefGoogle Scholar
  30. 30.
    Strieter, R. M., Chensue, S. W., Basha, M. A., Standiford, T. J., Lynch, J. P., Baggiolini, M., et al. (1990). Human alveolar macrophage gene expression of interleukin-8 by tumor necrosis factor-alpha, lipopolysaccharide, and interleukin-1 beta. American Journal of Respiratory Cell and Molecular Biology, 2, 321–326.PubMedCrossRefGoogle Scholar
  31. 31.
    Rossi, D., & Zlotnik, A. (2000). The biology of chemokines and their receptors. Annual Review of Immunology, 18, 217–242.PubMedCrossRefGoogle Scholar
  32. 32.
    Mukaida, N., Harada, A., & Matsushima, K. (1998). Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions. Cytokine & Growth Factor Reviews, 9, 9–23.CrossRefGoogle Scholar
  33. 33.
    Venturi, M. L., Attinger, C. E., Mesbahi, A. N., Hess, C. L., & Graw, K. S. (2005). Mechanisms and clinical applications of the vacuum-assisted closure (VAC) device: A review. American Journal of Clinical Dermatology, 6, 185–194.PubMedCrossRefGoogle Scholar
  34. 34.
    Leininger, B. E., Rasmussen, T. E., Smith, D. L., Jenkins, D. H., & Coppola, C. (2006). Experience with wound VAC and delayed primary closure of contaminated soft tissue injuries in Iraq. Journal of Trauma-Injury, Infection, and Critical Care, 61, 1207–1211.CrossRefGoogle Scholar
  35. 35.
    Norbury, K., & Kieswetter, K. (2007). Vacuum-assisted closure therapy attenuates the inflammatory response in a porcine acute wound healing model. WOUND, 19, 97–106.Google Scholar
  36. 36.
    Burchett, S. K., Weaver, W. M., Westall, J. A., Larsen, A., Kronheim, S., & Wilson, C. B. (1988). Regulation of tumor necrosis factor/cachectin and IL-1 secretion in human mononuclear phagocytes. The Journal of Immunology, 140, 3473–3481.PubMedGoogle Scholar
  37. 37.
    Fitzgerald, K. A., O’Nei, L. A. J., Gearin, A. J. H., & Callard, R. E. (Eds.). (2001). The cytokine factsbook (2nd ed.). San Diego: Academic Press.Google Scholar
  38. 38.
    Greene, A. K., Puder, M., Roy, R., Arsenault, D., Kwei, S., Moses, M. A., et al. (2006). Microdeformational wound therapy: Effects on angiogenesis and matrix metalloproteinases in chronic wounds of 3 debilitated patients. Annals of Plastic Surgery, 56, 418–422.PubMedCrossRefGoogle Scholar
  39. 39.
    Miller, L. S., O’Connell, R. M., Gutierrez, M. A., Pietras, E. M., Shahangian, A., Gross, C. E., et al. (2006). MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity, 24(1), 79–91.PubMedCrossRefGoogle Scholar
  40. 40.
    Mölne, L., Verdrengh, M., & Tarkowski, A. (2000). Role of neutrophil leukocytes in cutaneous infection caused by Staphylococcus aureus. Infection and Immunity, 68, 6162–6167.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Dularay, B., Elson, C. J., Clements-Jewery, S., Damais, C., & Lando, D. (1990). Recombinant human interleukin-1 beta primes human polymorphonuclear leukocytes for stimulus-induced myeloperoxidase release. Journal of Leukocyte Biology, 47, 158–163.PubMedGoogle Scholar
  42. 42.
    Borregaard, N. (2010). Neutrophils, from marrow to microbes. Immunity, 33, 657–670.PubMedCrossRefGoogle Scholar
  43. 43.
    Pradhan, L., Cai, X., Wu, S., Andersen, N. D., Martin, M., Malek, J., et al. (2011). Gene expression of pro-inflammatory cytokines and neuropeptides in diabetic wound healing. Journal of Surgical Research, 167(2), 336–342.PubMedCrossRefGoogle Scholar
  44. 44.
    Weed, T., Ratliff, C., & Drake, D. B. (2004). Quantifying bacterial bioburden during negative pressure wound therapy: Does the wound VAC enhance bacterial clearance? Annals of Plastic Surgery, 52, 276–279.PubMedCrossRefGoogle Scholar
  45. 45.
    Mouës, C. M., Vos, M. C., van den Bemd, G. J., Stijnen, T., & Hovius, S. E. (2004). Bacterial load in relation to vacuum-assisted closure wound therapy: A prospective randomized trial. Wound Repair and Regeneration, 12, 11–17.PubMedCrossRefGoogle Scholar
  46. 46.
    Borgquist, O., Ingemansson, R., & Malmsjo, M. (2010). Wound edge microvascular blood flow during negative-pressure wound therapy: Examining the effects of pressures from −10 to −175 mmHg. Plastic and Reconstructive Surgery, 125, 502–509.PubMedCrossRefGoogle Scholar
  47. 47.
    Venturi, M. L., Attinger, C. E., Mesbahi, A. N., Hess, C. L., & Graw, K. S. (2005). Mechanisms and clinical applications of the vacuum-assisted closure (VAC) device: A review. American Journal of Clinical Dermatology, 6, 185–194.PubMedCrossRefGoogle Scholar
  48. 48.
    Leininger, B. E., Rasmussen, T. E., Smith, D. L., Jenkins, D. H., & Coppola, C. (2006). Experience with wound VAC and delayed primary closure of contaminated soft tissue injuries in Iraq. Journal of Trauma-Injury, Infection, and Critical Care, 61, 1207–1211.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Daohong Liu
    • 1
  • Lihai Zhang
    • 1
  • Tongtong Li
    • 1
  • Guoqi Wang
    • 1
  • Hailong Du
    • 1
  • Hongping Hou
    • 1
  • Li Han
    • 2
    Email author
  • Peifu Tang
    • 1
    Email author
  1. 1.Department of OrthopaedicsThe Genearl Hospital of People’s Liberation ArmyBeijingChina
  2. 2.Center for Hospital Infection ControlChinese PLA Institute for Disease Control and PreventionBeijingChina

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