Lasers in Medical Science

, Volume 30, Issue 1, pp 117–126 | Cite as

Effect of low-level laser therapy on inflammatory mediator release during chemotherapy-induced oral mucositis: a randomized preliminary study

  • Geisa Badauy Lauria Silva
  • Nancy Tomoko Sacono
  • Angélica Ferreira Othon-Leite
  • Elismauro Francisco Mendonça
  • Adriano Moraes Arantes
  • César Bariani
  • Luciana Garcia Lobo Duarte
  • Mauro Henrique Nogueira Abreu
  • Celso Martins Queiroz-Júnior
  • Tarcília Aparecida Silva
  • Aline Carvalho BatistaEmail author
Original Article


Patients undergoing hematopoietic stem cell transplantation (HSCT) are submitted to a conditioning regimen of high-dose chemotherapy, with or without radiation therapy, which usually results in oral ulcerations and mucosal barrier breakdown. Oral mucositis (OM) is a common and debilitating toxicity side effect of autologous and allogeneic HSCT. The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) on the severity of OM and inflammatory mediator (TNF-α, IL-6, IL-1β, IL-10, TGF-β, metalloproteinases, and growth factors) levels in saliva and blood of HSCT patients. Thirty patients were randomly assigned to two groups: control (n = 15) and laser (n = 15). LLLT was applied from the first day of the conditioning regimen until day 7 post-HSCT (D + 7). Saliva and blood were collected from patients on admission (AD), D-1, D + 3, D + 7, and on marrow engraftment day (ME). Clinical results showed less severe OM in the laser group (p < 0.05). The LLLT group showed increased matrix metalloproteinase 2 (MMP-2) levels in saliva on D + 7 (p = 0.04). Significant differences were also observed for IL-10 on D + 7 and on ME in blood plasma, when compared to the control group (p < 0.05). No significant differences were seen in saliva or blood for the other inflammatory mediators investigated. LLLT was clinically effective in reducing the severity of chemotherapy-induced OM in HSCT patients, and its mechanism of action does not seem to be completely linked to the modulation of pro- or anti-inflammatory cytokines, growth factors or matrix metalloproteinases.


Mucositis Stomatitis Cancer chemotherapy protocol Hematopoietic stem cell transplant Laser therapy Cytokines 



This study was sponsored by grants from the Foundation for Research Support in the State of Goiás (FAPEG—Grant 2010102670007) and the National Council for Scientific and Technological Development (CNPq—Grant 479587/2010-8). The authors wish to thank Araújo Jorge Hospital, Goiás Cancer Combat Association, Goiânia, Brazil.

Conflict of interest

None declared.


  1. 1.
    Papas AS, Clark RE, Martuscelli G, O’Loughlin KT, Johansen E, Miller KB (2003) A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 31:705–712. doi: 10.1038/sj.bmt.1703870 PubMedCrossRefGoogle Scholar
  2. 2.
    Scully C, Epstein JB, Sonis ST (2003) Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and radiochemotherapy: part 1, pathogenesis and prophylaxis of mucositis. Head Neck 25:1057–1070. doi: 10.1002/hed.10318 PubMedCrossRefGoogle Scholar
  3. 3.
    Sonis ST, Oster G, Fuchs H, Bellm L, Bradford WZ, Edelsberg J et al (2001) Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol 19:2201–2205PubMedGoogle Scholar
  4. 4.
    Donnely JP, Muus P, Schattenberg A, de Witte T, Horrevorts A, De Pauw BE (1992) A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients. Bone Marrow Transplant 9:409–413Google Scholar
  5. 5.
    Blijlevens NM, Donnelly JP, De Pauw BE (2000) Mucosal barrier injury: biology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant 25:1269–1278. doi: 10.1038/sj.bmt.1702447 PubMedCrossRefGoogle Scholar
  6. 6.
    Raber-Durlacher JE, Elad S, Barasch A (2010) Oral mucositis. Oral Oncol 46:425–456. doi: 10.1016/j.oraloncology.2010.03.012 CrossRefGoogle Scholar
  7. 7.
    Vagliano L, Feraut C, Gobertto G, Trunfio A, Errico A, Campani V, Costazza G, Mega A et al (2011) Incidence and severity of oral mucositis in patients undergoing haematopoietic SCT-results of a multicentre study. Bone Marrow Transplant 46:727–732. doi: 10.1038/bmt.2010.184 PubMedCrossRefGoogle Scholar
  8. 8.
    Qutob AF, Gue S, Revesz T, Logan RM, Keefe D (2013) Prevention of oral mucositis in children receiving cancer therapy: a systematic review and evidence-based analysis. Oral Oncol 49:102–107. doi: 10.1016/j.oraloncology.2012.08.008 PubMedCrossRefGoogle Scholar
  9. 9.
    Elad S, Ackerstein A, Bitan M, Shapira MY, Resnick I, Gesundheit B et al (2006) A prospective, double-blind phase II study evaluating the safety and efficacy of a topical histamine gel for the prophylaxis of oral mucositis in patients post hematopoietic stem cell transplantation. Bone Marrow Transplant 37:757–762. doi: 10.1038/sj.bmt.1705331 PubMedCrossRefGoogle Scholar
  10. 10.
    Keefe DM, Schubert M, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE et al (2007) Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 109:820–831. doi: 10.1002/cncr.22484 PubMedCrossRefGoogle Scholar
  11. 11.
    Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein JB et al (2004) Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 100:2026–2046. doi: 10.1002/cncr.20163 PubMedCrossRefGoogle Scholar
  12. 12.
    Sonis ST (2004) The pathobiology of mucositis. Nat Rev Cancer 4:277–284. doi: 10.1038/nrc1318 PubMedCrossRefGoogle Scholar
  13. 13.
    Amaral TMP, Campos CC, Santos TPM, Leles CR, Teixeira AL, Teixeira MM et al (2012) Effect of salivary stimulation therapies on salivary flow and chemotherapy-induced mucositis: a preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol Oral Endod 113:628–637. doi: 10.1016/j.oooo.2011.10.012 CrossRefGoogle Scholar
  14. 14.
    Kreisler M, Christoffers AB, Al-Hah H, Willershausen B, d’Hoedt B (2002) Low level 809-nm diode laser-induced in vitro stimulation of the proliferation of human gingival fibroblast. Lasers Surg Med 30:365–369PubMedCrossRefGoogle Scholar
  15. 15.
    Demidova-Rice TN, Slomatina EV, Yaroslavsky AN, Herman IM, Hamblin MR (2007) Low-level light stimulates excisional wound healing in mice. Lasers Surg Med 39:706–715. doi: 10.1002/lsm.20549 PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Migliorati C, Hewson I, Lalla RV, Antunes HS, Estilo CL, Hodgson B et al (2013) Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer 21:333–341. doi: 10.1007/s00520-012-1605-6 PubMedCrossRefGoogle Scholar
  17. 17.
    Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DMK (2008) Serum levels of NFkB and proinflammatory cytokines following administration of mucotoxic drugs. Cancer Biol Ther 7:1139–1145. doi: 10.4161/cbt.7.7.6207 PubMedCrossRefGoogle Scholar
  18. 18.
    Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DMK (2009) Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered? Cancer Chemother Pharmacol 63:239–251. doi: 10.1007/s00280-008-0732-8 PubMedCrossRefGoogle Scholar
  19. 19.
    Silva GB, Mendonça EF, Bariani C, Antunes HS, Silva MA (2011) The prevention of induced oral mucositis with low-level laser therapy in bone marrow transplantation patients: a randomized clinical trial. Photomed Laser Surg 29:27–31. doi: 10.1089/pho.2009.2699 PubMedCrossRefGoogle Scholar
  20. 20.
    World Health Organization (1979) Handbook for reporting results of cancer treatment. Geneva World Health Organ 48:15–22Google Scholar
  21. 21.
    Antunes HS, de Azevedo AM, da Silva Bouzas LF, Adao CA, Pinheiro CT, Mayhe R et al (2007) Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: a randomized trial. Blood 109:2250–2255. doi: 10.1182/blood-2006-07-035022 PubMedCrossRefGoogle Scholar
  22. 22.
    Corazza AV, Jorge J, Kurachi C, Bagnato VS (2007) Photobiomodulation on the angiogenesis of skin wounds in rats using different light sources. Photomed Laser Surg 25:102–106. doi: 10.1089/pho.2006.2011 PubMedCrossRefGoogle Scholar
  23. 23.
    França CM, Núñz SC, Prates RA, Noborikawa E, Faria RM, Ribeiro MS (2009) Low-intensity red laser on the prevention and treatment of induced-oral mucositis in hamsters. J Photochem Photobiol B 94:25–31. doi: 10.1016/j.jphotobiol.2008.09.006 PubMedCrossRefGoogle Scholar
  24. 24.
    Meirovtz A, Kuten M, Billan S, Abdah-Bortnyak R, Sharon A, Peretz T et al (2010) Cytokines levels, severity of acute mucositis and need of PEG tube installation during chemo-radiation for head and neck cancer – a prospective pilot study. Radiat Oncol 5:16. doi: 10.1186/1748-717X-5-16 CrossRefGoogle Scholar
  25. 25.
    Lalla RV, Pilbeam CC, Walsh SJ, Sonis ST, Keefe DMK, Peterson DE (2010) Role of the cycloxygenase pathway in chemotherapy-induced oral mucositis: a pilot study. Support Care Cancer 18:95–103. doi: 10.1007/s00520-009-0635-1 PubMedCrossRefGoogle Scholar
  26. 26.
    Morales-Rojas T, Vieira N, Morón-Medina A, Alvares CJ, Alvares A (2012) Proinflammatory cytokines during the initial phase of oral mucositis in patients with acute lymphoblastic leukaemia. Int J Paedatr Dent 22:191–196. doi: 10.1111/j.1365-263X.2011.01175.x CrossRefGoogle Scholar
  27. 27.
    Efron PA, Moldawer LL (2004) Cytokines and wound healing: the role of cytokine and anticytokine therapy in the repair response. J Burn Care Rehabil 25:149–160PubMedCrossRefGoogle Scholar
  28. 28.
    Mateo RB, Reichner JS, Albina JE (1994) Interleukin-6 activity in wounds. Am J Physiol 266:1840–1844Google Scholar
  29. 29.
    Goodman L, Stein GH (1994) Basal and induced amounts of interleukin-6 mRNA decline progressive with age in human fibroblasts. J Biol Chem 269:19250–19255PubMedGoogle Scholar
  30. 30.
    Min CK, Lee WY, Min DJ, Lee DG, Kim YJ, Park YH et al (2001) The kinetics of circulating cytokines including IL-6, TNF-alpha, IL-8 and IL-10 following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 28:935–940PubMedCrossRefGoogle Scholar
  31. 31.
    Al-dasooqui N, Gigson RJ, Bowen JM, Keefe DM (2009) Matrix metalloproteinases: key regulators in the pathogenesis of chemotherapy-induced mucositis? Cancer Chemother Pharmacol 64:1–9. doi: 10.1007/s00280-009-0984-y CrossRefGoogle Scholar
  32. 32.
    Manicone AM, McGuire JK (2008) Matrix metalloproteinases as modulators of inflammation. Semin Cell Dev Biol 19:34–41. doi: 10.1016/j.semcdb.2007.07.003 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Geisa Badauy Lauria Silva
    • 1
    • 2
  • Nancy Tomoko Sacono
    • 2
  • Angélica Ferreira Othon-Leite
    • 2
  • Elismauro Francisco Mendonça
    • 2
  • Adriano Moraes Arantes
    • 1
  • César Bariani
    • 1
  • Luciana Garcia Lobo Duarte
    • 1
  • Mauro Henrique Nogueira Abreu
    • 3
  • Celso Martins Queiroz-Júnior
    • 4
  • Tarcília Aparecida Silva
    • 4
  • Aline Carvalho Batista
    • 2
    Email author
  1. 1.Hematopoietic Stem Cell Transplant Unit, Araújo Jorge HospitalAssociação de Combate ao Câncer de GoiásGoiâniaBrazil
  2. 2.Department of Stomatology (Oral Pathology), Dental SchoolFederal University of GoiásGoiâniaBrazil
  3. 3.Department of Preventive and Social Dentistry, Dental SchoolFederal University of Minas GeraisBelo HorizonteBrazil
  4. 4.Department of Oral Surgery and Pathology, Dental SchoolFederal University of Minas GeraisBelo HorizonteBrazil

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