Abstract
Hyperthermia is a condition characterized by increased body temperature as a consequence of failed thermoregulation. Hyperthermia occurs when a body produces or absorbs more heat than it dissipates. Hyperthermia also elicits various effects on the physiology of living cells. For instance, fever-range temperature (39 °C to 40 °C) can modulate the activities of immune cells, including antigen-presenting cells, Tcells, and natural killer cells. Heat shock temperature (41 °C to 43 °C) can increase the immunogenicity of tumor cells. Cytotoxic temperature (> 43 °C) can create an antigen source to induce an anti-tumor immune response. The immunomodulatory effect of hyperthermia has promoted an interest in hyperthermia-aided immunotherapy, particularly against tumors. Hyperthermia has also been used to treat deep fungal, bacterial, and viral skin infections. We conducted a series of open or controlled trials to treat skin human papillomavirus infection by inducing local hyperthermia. More than half of the patients were significantly cured compared with those in the control trial. A series of challenging clinical cases, such as large lesions in pregnant patients or patients with diabetes mellitus, were also successfully and safely managed using the proposed method. However, further studies should be conducted to clarify the underlying mechanisms and promote the clinical applications of hyperthermia.
Similar content being viewed by others
References
Gao XH, Chen HD. Hyperthermia: recognition, prevention and treatment. New York: Nova publishers, 2012
Horowitz M. Genomics and proteomics of heat acclimation. Front Biosci 2010; 2(1): 1068–1080
Patz JA, Campbell-Lendrum D, Holloway T, Foley JA. Impact of regional climate change on human health. Nature 2005; 438(7066): 310–317
Rowlands DJ, Frame DJ, Ackerley D, Aina T, Booth BBB, Christensen C, Collins M, Faull N, Forest CE, Grandey BS, Gryspeerdt E, Highwood EJ, Ingram WJ, Knight S, Lopez A, Massey N, McNamara F, Meinshausen N, Piani C, Rosier SM, Sanderson BM, Smith LA, Stone DA, Thurston M, Yamazaki K, Hiro Yamazaki Y, Allen MR. Broad range of 2050 warming from an observationally constrained large climate model ensemble. Nat Geosci 2012; 5(4): 256–260
Bouchama A, Knochel JP. Heat stroke. N Engl J Med 2002; 346(25): 1978–1988
Zhang HG, Mehta K, Cohen P, Guha C. Hyperthermia on immune regulation: a temperature’s story. Cancer Lett 2008; 271(2): 191–204
Hildebrandt B, Wust P, Ahlers O, Dieing A, Sreenivasa G, Kerner T, Felix R, Riess H. The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol 2002; 43(1): 33–56
Kourtis N, Nikoletopoulou V, Tavernarakis N. Small heat-shock proteins protect from heat-stroke-associated neurodegeneration. Nature 2012; 490(7419): 213–218
Kus-Liśkiewicz M, Polańska J, Korfanty J, Olbryt M, Vydra N, Toma A, Widłak W. Impact of heat shock transcription factor 1 on global gene expression profiles in cells which induce either cytoprotective or pro-apoptotic response following hyperthermia. BMC Genomics 2013; 14(1): 456
Sugimoto N, Shido O, Matsuzaki K, Ohno-Shosaku T, Hitomi Y, Tanaka M, Sawaki T, Fujita Y, Kawanami T, Masaki Y, Okazaki T, Nakamura H, Koizumi S, Yachie A, Umehara H. Cellular heat acclimation regulates cell growth, cell morphology, mitogenactivated protein kinase activation, and expression of aquaporins in mouse fibroblast cells. Cell Physiol Biochem 2012; 30(2): 450–457
Binder RJ, Vatner R, Srivastava P. The heat-shock protein receptors: some answers and more questions. Tissue Antigens 2004; 64(4): 442–451
Chen W, Syldath U, Bellmann K, Burkart V, Kolb H. Human 60-kDa heat-shock protein: a danger signal to the innate immune system. J Immunol 1999; 162(6): 3212–3219
Panjwani NN, Popova L, Srivastava PK. Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs. J Immunol 2002; 168(6): 2997–3003
Lehner T, Bergmeier LA, Wang Y, Tao L, Sing M, Spallek R, van der Zee R. Heat shock proteins generate beta-chemokines which function as innate adjuvants enhancing adaptive immunity. Eur J Immunol 2000; 30(2): 594–603
Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturationsignal to dendritic cells and activate the NF-kappa B pathway. Int Immunol 2002; 12(11): 1539–1546
Singh-Jasuja H, Scherer HU, Hilf N, Arnold-Schild D, Rammensee HG, Toes RE, Schild H. The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor. Eur J Immunol 2000; 30(8): 2211–2215
Binder RJ, Anderson KM, Basu S, Srivastava PK. Cutting edge: heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo. J Immunol 2000; 165(11): 6029–6035
Wells AD, Malkovsky M. Heat shock proteins, tumor immunogenicity and antigen presentation: an integrated view. Immunol Today 2000; 21(3): 129–132 PMID:10689300
Jones EL, Samulski TV, Vujaskovic Z, Prosnitz LR, Dewhirst MW. Hyperthermia. In: Halperin EC, Perez CA, Brady LW. Principles and Practice of Radiation Oncology. Philadelphia: Lippincott Williams & Wilkins, 2008: 637–668
Sneed PK, Hsu IC. Hyperthermia. In: Ko AH, Dollinger M, Rosenbaum EH. Everyone’s Guide to Cancer Therapy: How Cancer is Diagnosed, Treated, and Managed Day to Day. Kansas: Andrews McMeel Publishing, 2008: 98–100
Bicher JI, Al-Bussam N, Wolfstein RS. Thermoradiotherapy with curative intent-breast, head, neck and prostate tumors. Dtsch Z Onkol 2006; 38(3): 116–122
Bos JD. Skin Immune System: Cutaneous Immunology and Clinical Immunodermatology. 3rd ed. Florida: CRC Press, 2004
Li X, Gao XH, Jin L, Wang Y, Hong Y, McHepange UO, Wang X, Jiang Y, Wei H, Chen HD. Local hyperthermia could induce migrational maturation of Langerhans cells in condyloma acuminatum. J Dermatol Sci 2009; 54(2): 121–123
Wang X, Gao XH, Li X, Hong Y, Qi R, Chen HD, Zhang L, Wei H. Local hyperthermia induces apoptosis of keratinocytes in both normal skin and condyloma acuminata via different pathways. Apoptosis 2009; 14(5): 721–728
Zhu LL, Gao XH, Qi R, Hong Y, Li X, Wang X, McHepange UO, Zhang L, Wei H, Chen HD. Local hyperthermia could induce endogenous interferons gene expression via JAK-STATs signaling pathway in condyloma acuminate. Antiviral Res 2010; 88(2): 187–192
Huo W, Li GH, Qi RQ, Zhang L, Yan XX, Chen HD, Gao XH. Clinical and immunologic results of local hyperthermia at 44 °C for extensive genital warts in patients with diabetes mellitus. Int J Hyperthermia 2013; 29(1): 17–20
Zhang L, Wang YR, Hong YX, Xu YQ, Zhang L, Li XD, Xiao T, Lu DQ, Chen HD, Gao XH. Temporal effect of local hyperthermia on murine contact hypersensitivity. Chin Med J (Engl) 2013; 126(8): 1555–1559
zur Hausen H. Papillomaviruses-to vaccination and beyond. Biochemistry (Mosc) 2008; 73(5): 498–503
Huo W, Gao XH, Sun XP, Qi RQ, Hong Y, Mchepange UO, Li XD, Xiao BH, Lin JP, Jiang Y, Zhang L, Li YH, Xiao T, Chen JZ, Chen HD. Local hyperthermia at 44 °C for the treatment of plantar warts: a randomized, patient-blinded, placebo-controlled trial. J Infect Dis 2010; 201(8): 1169–1172
Li XD, Zhang C, Hong YX, Zhang DS, Wei HC, Chen HD, Gao XH. Local hyperthermia treatment of extensive viral warts in Darier disease: a case report and literature review. Int J Hyperthermia 2012; 28(5): 451–455
Ma Y, Huo W, Hong YX, Chen HD, Gao XH. Successful clearance of facial warts with local hyperthermia. Dermatol Ther 2012; 25(4): 386–388
Huo W, Di ZH, Xiao BH, Qi RQ, Weiland M, Gao XH. Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report. Dermatol Ther 2013. [Epub ahead of print]. doi: 10.1111/dth.12066
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gao, X., Chen, H. Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected skin diseases. Front. Med. 8, 1–5 (2014). https://doi.org/10.1007/s11684-014-0309-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11684-014-0309-3