Effect of Low-Level Laser Therapy (LLLT) in Pulmonary Inflammation in Asthma Induced by House Dust Mite (HDM): Dosimetry Study

Nicole Cristine Rigonato-Oliveira, Auriléia Aparecida de Brito, Luana Beatriz Vitoretti, Gabriel de Cunha Moraes, Tawany Gonçalves, Karine Zanella Herculano, Cintia Estefano Alves, Adriana Lino-Dos-Santos-Franco, Flávio Aimbire, Rodolfo Paula Vieira, Ana Paula Ligeiro de Oliveira, Nicole Cristine Rigonato-Oliveira, Auriléia Aparecida de Brito, Luana Beatriz Vitoretti, Gabriel de Cunha Moraes, Tawany Gonçalves, Karine Zanella Herculano, Cintia Estefano Alves, Adriana Lino-Dos-Santos-Franco, Flávio Aimbire, Rodolfo Paula Vieira, Ana Paula Ligeiro de Oliveira

Abstract

Asthma is characterized by chronic inflammation in the airways. Several models have been proposed for the discovery of new therapies. Low-Level Laser Therapy (LLLT) is relatively new and effective, very low cost, with no side effects. However, there is still no consensus on the optimal dose to be used. In this sense, the objective of the present study was to evaluate the best dose in an experimental model of asthma induced by House Dust Mite (HDM). Balb/c mice received administration of 100 ug/animal HDM and LLLT applications (diode laser: 660 nm, 100 mW and four different energies 1J, 3J, 5J, and 7.5J) for 16 days. After 24 hours, we studied inflammatory, functional, and structural parameters. The results showed that LBI was able to modulate the pulmonary inflammation observed by reducing the number of cells in Bronchoalveolar Lavage Fluid (BALF) as well as reducing the percentage of neutrophils, eosinophils and T lymphocytes. On the other hand, LLLT increased the level of IL-10 and reduced levels of IL-4, IL-5 and IL-13 in BALF. LLLT was able to reduce the production of mucus, peribronchial eosinophils, collagen deposition, bronchoconstriction index, and bronchial and muscular thickening in the airways. We concluded that the use of LLLT in the treatment of chronic inflammation of the airways attenuated the inflammatory process and functional and structural parameters. We emphasize, in general, that the 1J and 3J laser presented better results. Thus, photobiomodulation may be considered a promising tool for the treatment of chronic pulmonary allergic inflammation observed in asthma.

Figures

Figure 1
Figure 1
Effect of LLLT on the total number of cells (a) and the number of macrophages (b), lymphocytes (c), neutrophils (d), and eosinophils (e) recovered from the BALF. The groups used in the experiment were Basal (unmanaged animals), asthmatics (HDM) (animals immunized and challenged with HDM), LLLT (animals only treated with LLLT), and HDM+LLLT (animals sensitized and challenged with HDM and subsequently treated with LLLT). The results refer to the use of 10 mice in each experimental group. Values expressed as mean and standard deviation. # p θ p <0.001, ϕ p <0.01, and δ p <0.05 when compared to the asthmatic group (HDM) and ns (not significant); ∗ p<0,05 and ∗∗∗ p<0,001 when compared HDM+LLLT (3J) group with the other groups treated with other doses.
Figure 2
Figure 2
Effect of LLLT on IL-4 (a), IL-5 (b), IL-10 (c), and IL-13 (d) levels in BALF supernatant. Values expressed as mean and standard deviation. The groups used in the experiment are described in Figure 1. The results refer to the use of 10 mice in each experimental group. # p #∗ p <0.01 when compared to the Basal group; θ p <0.001, Δ p <0.01, and ϕ p <0.05 when compared to the asthmatic group (HDM) and ns (not significant); ∗ p<0,05 and ∗∗∗ p<0,001 when compared HDM+LLLT (3J) group with the other groups treated with other doses.
Figure 3
Figure 3
Effect of LLLT on the quantification of peribronchial eosinophils. The lungs were fixed, prepared, and stained with LUNA for the analysis of eosinophils in the airways. The animals were irradiated with LLLT 3x/week for 5 weeks, 1 hour after challenge with HDM. Increase of × 400. Values expressed as mean and standard deviation. The groups used in the experiment are described in Figure 1. The results refer to the use of 10 mice in each experimental group. # p θ p <0.001 when compared to the asthmatic group (HDM) and ns (not significant); ∗ p<0,05 and ∗∗∗ p<0,001 when compared HDM+LLLT (3J) group with the other groups treated with other doses.
Figure 4
Figure 4
Effect of LLLT on the production of mucus in the airways. The lungs were fixed, prepared, and stained with PAS (Periodic Acid Schif) for the analysis of mucus in the airways. The animals were irradiated with LLLT 3x/week for 5 weeks, 1 hour after challenge with HDM. Increase of × 200. Values expressed as mean and standard deviation. The groups used in the experiment are described in Figure 1. The results refer to the use of 10 mice in each experimental group. # p ∗ p<0,05 and ∗∗ p<0,01 when compared HDM+LLLT (3J) group with the other groups treated with other doses.
Figure 5
Figure 5
Effect of LLLT on the production of collagen in the airways. The lungs were fixed, prepared, and stained with PSR for analysis of collagen in the airways. The animals were irradiated with LLLT 3x/week for 5 weeks, 1 hour after challenge with HDM. Increase of × 200. Values expressed as mean and standard deviation. The groups used in the experiment are described in Figure 1. The results refer to the use of 10 mice in each experimental group. # p ∗ p<0,05 when compared HDM+LLLT (3J) group with the other groups treated with other doses.
Figure 6
Figure 6
Effect of LLLT on bronchoconstriction index. The lungs were fixed, prepared and stained with HE for analysis of bronchoconstriction index in the airways. Increase of × 400. Values expressed as mean and standard deviation. The groups used in the experiment are described in Figure 1. The results refer to the use of 10 mice in each experimental group. # p θ p <0.001, Δ p <0.01, and ϕ p <0.05 when compared to the asthmatic group (HDM); ∗ p<0,05 when compared HDM+LLLT (3J) group with the other groups treated with other doses.
Figure 7
Figure 7
Effect of LLLT on bronchial thickening and airway smooth muscle thickening. The lungs were fixed, prepared and stained with HE for the above analyzes. Increase of × 400. Values expressed as mean and standard deviation. The groups used in the experiment are described in Figure 1. The results refer to the use of 10 mice in each experimental group. # p θ p <0.001 when compared to the asthmatic group (HDM) and ns (not significant) when compared HDM+LLLT (3J) group with the other groups treated with other doses.

References

    1. GINA. Global Initiative for Asthma. Strategy for Asthma management and prevention, 2018, .
    1. Lozano R., Naghavi M., Foreman K., et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380(9859):2095–2128. doi: 10.1016/S0140-6736(12)61728-0.
    1. Mikhailov V. A., Aleksandrova O., Gol'dina E. M. The immunomodulating action of low-energy laser radiation in the treatment of bronchial asthma. Voprosy Kurortologii, Fizioterapii, I Lechebnoĭ Fizicheskoĭ Kultury. 1998;4:23–25.
    1. Carvalho J. L., Britto A., de Oliveira A. P. L., et al. Beneficial effect of low-level laser therapy in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling. Lasers in Medical Science. 2017;32(2):305–315. doi: 10.1007/s10103-016-2115-4.
    1. Da Silva C. M., Leal M. P., Brochetti R. A., et al. Low level laser therapy reduces the development of lung inflammation induced by formaldehyde exposure. PLoS ONE. 2015;10(11, article e0142816)
    1. da Cunha Moraes G., Vitoretti L. B., de Brito A. A., et al. Low-level laser therapy reduces lung inflammation in an experimental model of chronic obstructive pulmonary disease involving P2X7 receptor. Oxidative Medicine and Cellular Longevity. 2018;2018:8. doi: 10.1155/2018/6798238.6798238
    1. Brochetti R. A., Leal M. P., Rodrigues R., et al. Photobiomodulation therapy improves both inflammatory and fibrotic parameters in experimentalmodel of lung fibrosis in mice. Lasers in Medical Science. 2017;32(8):1825–1834. doi: 10.1007/s10103-017-2281-z.
    1. Choi B., Chang M. S., Kim H. Y., et al. Effects of low level laser therapy on ovalbumin-induced mouse model of allergic rhinitis. Evidence-Based Complementary and Alternative Medicine. 2013;2013:8. doi: 10.1155/2013/753829.753829
    1. Silva V. R., Marcondes P., Silva M., et al. Low-level laser therapy inhibits bronchoconstriction, Th2 inflammation and airway remodeling in allergic asthma. Respiratory Physiology & Neurobiology. 2014;194(1):37–48. doi: 10.1016/j.resp.2014.01.008.
    1. Costa Carvalho J. L., de Brito A. A., de Oliveira A. P. L., et al. The chemokines secretion and the oxidative stress are targets of low-level laser therapy in allergic lung inflammation. Journal of Biophotonics. 2016;9(11-12):1208–1221. doi: 10.1002/jbio.201600061.
    1. Elseify M. Y., Mohammed N. H., Alsharkawy A. A., Elseoudy M. E. Laser acupuncture in treatment of childhood bronchial asthma. Journal of complementary and integrative medicine. 2013;10
    1. Dabbous O. A., Soliman M. M., Mohamed N. H., et al. Evaluation of the improvement effect of laser acupuncture biostimulation in asthmatic children by exhaled inflammatory biomarker level of nitric oxide. Lasers in Medical Science. 2017;32(1):53–59. doi: 10.1007/s10103-016-2082-9.
    1. Robinson D. S. Regulatory T cells and asthma. Clinical & Experimental Allergy. 2009;39(9):1314–1323. doi: 10.1111/j.1365-2222.2009.03301.x.
    1. Kumar M. N. K., Zhou C., Wu M. X. Laser-facilitated epicutaneous immunotherapy to IgE-mediated allergy. Journal of Controlled Release. 2016;235:82–90. doi: 10.1016/j.jconrel.2016.05.057.
    1. de Oliveira A. P., Peron J. P., Damazo A. S., et al. Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats. Respiratory Research. 2010;11, article 115
    1. Vieira R. P., Claudino R. C., Duarte A. C. S., et al. Aerobic exercise decreases chronic allergic lung inflammation and airway remodeling in mice. American Journal of Respiratory and Critical Care Medicine. 2007;176(9):871–877. doi: 10.1164/rccm.200610-1567OC.
    1. Debeuf N., Haspeslagh E., van Helden M., Hammad H., Lambrecht B. N. Mouse Models of Asthma. Current Protocols in Mouse Biology. 2016;6(2):169–184. doi: 10.1002/cpmo.4.
    1. Fritzsching B., Hagner M., Dai L., et al. Impaired mucus clearance exacerbates allergen-induced type 2 airway inflammation in juvenile mice. The Journal of Allergy and Clinical Immunology. 2017;140(1):190–203.e5. doi: 10.1016/j.jaci.2016.09.045.
    1. Zhou-Suckow Z., Duerr J., Hagner M., Mall M. A. Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases. Cell and Tissue Research. 2017;367(3):537–550. doi: 10.1007/s00441-016-2562-z.
    1. Piyadasa H., Altieri A., Basu S., Schwartz J., Halayko A. J., Mookherjee N. Biosignature for airway inflammation in a house dust mite-challenged murine model of allergic asthma. Biology Open. 2016;5(2):112–121. doi: 10.1242/bio.014464.
    1. Bax H. J., Keeble A. H., Gould H. J. Cytokinergic IgE action in mast cell activation. Frontiers in Immunology. 2012;3, article 229
    1. Zoltowska A. M., Lei Y., Fuchs B., Rask C., Adner M., Nilsson G. P. The interleukin-33 receptor ST2 is important for the development of peripheral airway hyperresponsiveness and inflammation in a house dust mite mouse model of asthma. Clinical & Experimental Allergy. 2016;46(3):479–490. doi: 10.1111/cea.12683.
    1. Wang X.-Y., Ma W.-J., Liu C.-S., Li Y.-X. Effect of low-level laser therapy on allergic asthma in rats. Lasers in Medical Science. 2014;29(3):1043–1050. doi: 10.1007/s10103-013-1456-5.
    1. Al-Muhsen S., Johnson J. R., Hamid Q. Remodeling in asthma. The Journal of Allergy and Clinical Immunology. 2011;128(3):451–462. doi: 10.1016/j.jaci.2011.04.047.
    1. Sojka D. K., Huang Y.-H., Fowell D. J. Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target. The Journal of Immunology. 2008;124(1):13–22. doi: 10.1111/j.1365-2567.2008.02813.x.

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