Research article
Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells
Published: 23 March 2012
Abstract (provisional)
Background
Interactions between the immune response and brain functions such as olfactory, auditory,
and visual sensations are likely. This study investigated the effect of sounds on
alloimmune responses in a murine model of cardiac allograft transplantation.
Methods
Naive CBA mice (H2k) underwent transplantation of a C57BL/6 (B6, H2b) heart and were
exposed to one of three types of music--opera (La Traviata), classical (Mozart), and
New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally,
we prepared two groups of CBA recipients with tympanic membrane perforation exposed
to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation
(pre-treatment). An adoptive transfer study was performed to determine whether regulatory
cells were generated in allograft recipients. Immunohistochemical, cell-proliferation,
cytokine, and flow cytometry assessments were also performed.
Results
CBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had
significantly prolonged allograft survival (median survival times [MSTs], 26.5 and
20 days, respectively), whereas those exposed to a single sound frequency (100, 500,
1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and
11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and
CBA recipients exposed to opera for 7 days before transplantation (pre-treatment)
rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive
transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary
allograft recipients resulted in significantly prolonged allograft survival in naive
secondary recipients (MSTs, 36, 68, and >100 days, respectively). Proliferation of
splenocytes, interleukin (IL)-2 and interferon (IFN)-gamma production was suppressed
in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant
recipients increased compared to that from splenocytes of untreated recipients. Flow
cytometry studies showed an increased CD4+CD25+Foxp3+ cell population in splenocytes
from those mice.
Conclusion
Our findings indicate that exposure to opera music, such as La traviata, could affect
such aspects of the peripheral immune response as generation of regulatory CD4+CD25+
cells and up-regulation of anti-inflammatory cytokines, resulting in prolonged allograft
survival.
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