title: Music exposure induced prolongation of cardiac allograft survival and generated regulatory CD4⁺ cells in mice.
abstract: In clinical practice, music has been used to decrease stress, heart rate, and blood pressure and to provide a distraction from disease symptoms. We investigated sound effects on alloimmune responses in murine heart transplantation. Naïve and eardrum-ruptured CBA/N (CBA, H2(K)) underwent transplantation of a C57BL/6 (B6, H2(b)) heart and were exposed to 1 of 3 types of music-opera (La Traviata), classical (Mozart), and New Age (Enya)-or 1 of 6 different single sound frequencies for 7 days. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 graft exposed to opera and classical music had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to 6 single sound frequencies and New Age did not (MSTs, 7, 8, 9, 8, 8, 8, and 11 days, respectively). Untreated and eardrum-ruptured CBA rejected B6 grafts acutely (MSTs, 7 and 8.5 days, respectively). Adoptive transfer of whole splenocytes, CD4(+) cells, and CD4(+)CD25(+) cells from opera-exposed primary recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and >50 days, respectively). Cell-proliferation, interleukin (IL)-2 and interferon-γ were suppressed in opera-exposed mice, whereas IL-4 and IL-10 from opera-exposed recipients were up-regulated. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population in splenocytes from opera-exposed mice. In conclusion, exposure to some types of music may induce prolonged survival of fully allogeneic cardiac allografts and generate CD4(+)CD25(+)Foxp3(+) regulatory cells.
authors.affiliation: Department of Cardiovascular Surgery, Juntendo University Hospital, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Uchiyama
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Amano
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Niimi
mesh_terms: D000161:Acoustic Stimulation; D019264:Adoptive Transfer; D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D006648:Histocompatibility; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009146:Music; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D013997:Time Factors; D018058:Tympanic Membrane Perforation / Q000276:immunology / Q000503:physiopathology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit