Melatonin: clinical prospects in immunology
Abstract
Introduction. For a long time, HIV has been associated with a number of inflammatory, infectious and neoplastic skin diseases. In the era of anti-retroviral therapy researchers have found even more about the relationship between skin disease and chronic immunosuppression. In particular, clinicians continue to face the trend of difficult-to-control viral infections, chronic skin inflammation and itching in people living with HIV.
Objectives. This article summarizes the latest updates in immunology, dermatology and HIV, revealing potential of the prospective substance melatonin and its efficacy in treating herpesvirus skin diseases as an alternative immunomodulator.
Materials and methods. A comprehensive literature search was carried out in July 2020 using electronic databases PubMed, EMBASE, MEDLINE, U.S. National Library of Medicine Clinical Trials, ResearchGate, and Cocharane Library.
Results. This review includes 24 articles, that demonstrated the modulating properties of melatonin and have established its effectiveness in the treatment of diseases associated with immunodeficiency conditions. Melatonin has been shown to have a regulatory effect on the immune system and directly enhance the immune response by improving the proliferation and maturation of natural killers, T and B lymphocytes, granulocytes and monocytes, and activates complement receptors.
Conclusions. Currently, the course of dermatological manifestations associated with herpes viruses, unfortunately, remains unfavorable and persists with high mortality coefficients, so the development of new approaches to the provision of medical care to HIV-infected patients is still relevant. Recent scientific studies indicate the high effectiveness of melatonin in the treatment of diseases accompanied by immunodeficiency. Researching of its effects in the dermatological manifestations of herpesvirus infections on the background of HIV is prospective and necessary for expand drug provision, treating comorbid conditions and improving the quality of life of each patient.
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References
Munawwar, A., Singh S. (2016). Human Herpesviruses as Copathogens of HIV Infection, Their Role in HIV Transmission, and Disease Progression. Journal of Laboratory Physicians. Jan-Jun; 8 (1), 5–18. doi: 10.4103/0974-2727.176228
Roizman, B. (1996). Herpesviridae. Fields Virology 3rd ed. (B. N. Fields, D. M. Knipe, P. M. Howley et al., eds.), Lippencott-Raven, Philadelphia, 2221–2230. https://scholar.google.com/scholar_lookup?title=Herpesviridae&author=B..%20Roizman&pages=2221-2230&publication_year=1996
Mettenleiter, T. C., Klupp, B. G., Granzow, H. (2009). Herpesvirus assembly: An update. Virus Res. 143 (2), 222–34. doi: 10.1016/j.virusres.2009.03.018.
Davison, A. J. (2010). Herpesvirus systematics. Vet Microbiol. 143, 52–69. doi: 10.1016/j.vetmic.2010.02.014
Davison, A. J. (2007). Overview of classification. Chapter 1. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge University Press, 1–8. https://www.ncbi.nlm.nih.gov/books/NBK47406/
Masur, H., Michelis, M. A., Greene, J. B., Onorato, I., Stouwe, R. A. V., Holzman, R. S., Wormser, G., Brettman, L., Lange, M., Murray, H. W., Cunningham, R. S. (1981). An outbreak of community acquired pneumocystis carinii pneumonia: inital manifestation of cellular immune dysfunction. N Engl J Med. 305, 1431–1438. doi: 10.1056/NEJM198112103052402
I. I. Mavrov. (2007). Osnovy diagnostiki i lecheniya v dermatologii i venerologii. Posobie dlya vrachej, internov i studentov. 792, 310.
Gross, G., Stephen, K. (2011). Sexually Transmitted Infections and Sexually Transmitted Diseases. Springer-Verlag Berlin Heidelberg. 301–318. https://www.springer.com/gp/book/9783642146626#aboutAuthors
Saple. D. S., Maniar, J. K., (1994). AIDS. Textbook and Atlas of Dermatology. 1st ed. Bhalani; Bombay. 1283-1299. https://scholar.google.com/scholar_lookup?title=IADVL+Textbook+and+Atlas+of+Dermatology&author=DS+Saple&author=JK+Maniar&publication_year=1994&
Highet A. S, Kurtz, J. (1995). Cutaneous manifestations of opportunistic infections in patients infected with human immunodeficiency virus. Viral infections. Textbook of Dermatology. 5th ed. Blackwell Scientific Publication. pp. 867–951. Clinical Microbiology Reviews. 440–450. PMCID: PMC174635. PMID: 7553576
Bauer, M. E., De la Fuente, M. (2016). The role of oxidative and inflammatory stress and persistent viral infections in immunosenescence. Role of Antioxidants and Natural Products in Inflammation. Oxid Med Cell Longev.158: 27-37. 5276130.
Grossman, M. C., Grossman, M. E. (1993). Chronic hyperkeratotic herpes zoster and human immunodeficiency virus infection (review). J Am Acad Dermatol. 306-308. doi: 10.1016/0190-9622(93)70041-q
Serinsöz, Fend. (2017). Human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) related lymphomas, pathology view point. Semin Diagn Pathol. 34 (4), 352–363. doi: 10.1053/j.semdp.2017.04.003
Treatments, Li, Zuo, et al. (2019). Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel. International Journal of Molecular Sciences. 20 (18), 4472. doi: 10.3390 / ijms20184472
Bubenik, G. A., Smith, P. S., Schams, D. (1986). The Effect of Orally Administered Melatonin on the Seasonality of Deer Pelage Exchange, Antler Development, LH, FSH, Prolactin, Testosterone, T3, T4, Cortisol, and Alkaline Phosphatase. J. Pineal Res. 3, 331–349. doi: 10.1111/j.1600-079X.1986.tb00756.x
Hameed, E. N. (2019). Melatonin Improves Erythropoietin Hyporesponsiveness via Suppression of Inflammation. Rev Recent Clin Trials. 14 (3), 203–208. doi: 10.2174/1574887114666190528120357
N Kouhi Habibi, A Shabestani Monfared, K Ebrahimnejad Gorji. (2018). The Protective Effects of Melatonin on Blood Cell Counts of Rectal Cancer Patients Following Radio-Chemotherapy: A Randomized Controlled Trial. Clin Transl Oncol. 2019 Jun;21 (6), 745–752. doi: 10.1007/s12094-018-1977-2. Epub 2018 Nov 12.
Slominski, A., Pisarchik, A., Semak, I., Sweatman, T., Wortsman, J., Szczesniewski, A., Slugocki, G., McNulty, J., Kauser, S., Tobin, D.J., et al. (2002). Serotoninergic and melatoninergic systems are fully expressed in human skin. FASEB J. 16, 896–898. doi: 10.1096/fj.01-0952fje
Gaudet, S. J., Slominski, A., Etminan, M., Pruski, D., Paus, R., Namboodiri, M. A. A. (1993). Identification and characterization of two isozymic forms of arylamine n-acetyltransferase in syrian hamster skin. J. Investig. Dermatol. 101, 660–665. doi: 10.1111/1523-1747.ep12371672
Helen, F., Galley, Andrea, Woolneret, al. (2018). Melatonin in Pregnancy (MEL-P2). US National Library of Medicine. NCT03609086.
M. Kadena, Y. Kumagai, A. Vandenbon, H. Matsushima, H. Fukamachi, N. Maruta, et al. (2017). Microarray and gene co-expression analysis reveals that melatonin attenuates immune responses and modulates actin rearrangement in macrophages. Biochem Biophys Res Commun, 485, 414–420. doi: 10.1016/j.bbrc.2017.02.063
P. Lissoni, S. Barni, A. Ardizzoia. A. (1994). Randomized Study With the Pineal Hormone Melatonin Versus Supportive Care Alone in Patients With Brain Metastases Due to Solid Neoplasms. ACS Journals. Cancer. Feb 1, 73 (3), 699–701.
doi: 10.1002/1097-0142(19940201)73:3<699::aid-cncr2820730332>3.0.co;2-l
P. Lissoni, F Rovelli, F Malugani. (2001). Anti-angiogenic Activity of Melatonin in Advanced Cancer Patients. Neuro Endocrinol Lett. 22 (1), 45–7. PMID: 11335879
P. Lissoni. Biochemotherapy (2007). With Standard Chemotherapies Plus the Pineal Hormone Melatonin in the Treatment of Advanced Solid Neoplasms. Pathol Biol (Paris). Apr-May 55 (3–4), 201–4. doi: 10.1016/j.patbio.2006.12.025. Epub 2007 Apr 18.
P. Lissoni, M. Chilelli, S. Villa. (2003). Five Years Survival in Metastatic Non-Small Cell Lung Cancer Patients Treated With Chemotherapy Alone or Chemotherapy and Melatonin: A Randomized Trial. J Pineal Res. Aug; 35 (1), 12–5. doi: 10.1034/j.1600-079x.2003.00032.x
Kittipong Onseng, Nutjaree Pratheepawanit Johns. (2017). Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation. J Altern Complement Med. Dec; 23 (12), 957–963. doi: 10.1089/acm.2017.0081
Merav A. Ben-David, Ruth Elkayam, Ilana Gelernter. (2016). Melatonin for Prevention of Breast Radiation Dermatitis: A Phase II, Prospective, Double-Blind Randomized Trial. Isr Med Assoc J. Mar-Apr 18 (3–4), 188–92. PMID: 27228641
Odilon da Silva Nunes. (2008). Regression of herpes viral infection symptoms using melatonin and SB-73: Comparison with Acyclovir. J Pineal Res. May; 44 (4), 373–-8.
doi: 10.1111/j.1600-079X.2007.00538.x
F. R. Nerone et al.(2019). Effects of Melatonin on Metabolic Abnormalities in HIV Patients Treated with Antiretroviral Drugs. Journal of Advances in Medical and Pharmaceutical Sciences, 21 (1), 1–10. Article no. JAMPS.49734 ISSN: 2394–1111
Gabriela B. Gelaleti, Thaiz F Borin, Larissa B Maschio-Signorin. (2017). Efficacy of melatonin, IL-25 and siIL-17B in tumorigenesis-associated properties of breast cancer cell lines. Life Sci. Aug 15;183, 98–109. doi: 10.1016/j.lfs.2017.06.013. Epub 2017 Jun 15.
P. Lissonil, S. Barnil, G. Tancinil. (1994). A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer. Jan; 69 (1), 196–9. doi: 10.1038/bjc.1994.34
A. G. de Matos Cavalcante. (2012). Melatonin Reduces Lung Oxidative Stress in Patients With Chronic Obstructive Pulmonary Disease: A Randomized, Double-Blind, Placebo-Controlled Study. J Pineal Res. Oct; 53 (3), 238–44. doi: 10.1111/j.1600-079X.2012.00992.x
M Alamili. (2013). Melatonin Suppresses Markers of Inflammation and Oxidative Damage in a Human Daytime Endotoxemia Model. J Crit Care. 2014 Feb; 29(1):184.e9-184.e13. doi:10.1016/j.jcrc.2013.09.006. Epub 2013 Oct 17.
N. M. Alamdari. (2015). A Double-Blind, Placebo-Controlled Trial Related to the Effects of Melatonin on Oxidative Stress and Inflammatory Parameters of Obese Women. Horm Metab Res. Jun; 47 (7), 504-8. doi: 10.1055/s-0034-1384587. Epub 2014 Aug 15.
B Hernández-Velázquez. (2016). Effects of Melatonin on the Acute Inflammatory Response Associated With Endoscopic Retrograde Cholangiopancreatography: A Randomized, Double-Blind, Placebo-Controlled Trial. Rev Gastroenterol Mex. Jul-Sep 81 (3), 141-8. doi: 10.1016/j.rgmx.2016.03.003. Epub 2016 Jun 16.
Z Zhao. (2018). The Protective Effect of Melatonin on Brain Ischemia and Reperfusion in Rats and Humans: In Vivo Assessment and a Randomized Controlled Trial. J Pineal Res. Nov; 65 (4), e12521.
doi: 10.1111/jpi.12521. Epub 2018 Sep 30.
Sánchez-López, A. L. (2018). Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis. Arch Med Res. Aug; 49 (6), 391–398. doi: 10.1016/j.arcmed.2018.12.004. Epub 2018 Dec 27.
Yosefifard, M. A. (2019). Randomized Control Trial Study to Determine the Effect of Melatonin on Serum Levels of IL-1β and TNF-α in Patients with Multiple Sclerosis. Iranian journal of allergy, asthma and immunology, 18 (6), 649–654.
Panah, F. (2019). The Effect of Oral Melatonin on Renal Ischemia-Reperfusion Injury in Transplant Patients: A Double-Blind, Randomized Controlled Trial. Transpl Immunol. Dec; 57, 101241. doi: 10.1016/j.trim.2019.101241. Epub 2019 Aug 22.
Bazyar, H. (2019). The Effects of Melatonin Supplementation in Adjunct With Non-Surgical Periodontal Therapy on Periodontal Status, Serum Melatonin and Inflammatory Markers in Type 2 Diabetes Mellitus Patients With Chronic Periodontitis: A Double-Blind, Placebo-Controlled Trial. Inflammopharmacology. Feb; 27 (1), 67–76. doi: 10.1007/s10787-018-0539-0
Stashkevich, D. S., Filippova, Y. U., Burmistrova, A. L. (2016). Aktual'nye voprosy immunologii: sistema citokinov, biologicheskoe znachenie, geneticheskij polimorfizm, metody opredeleniya: ucheb. posobie. CHelyabinsk Cicero, 8–15.
Neri, B., V de Leonardis, Gemelli, M. T. (1998). Melatonin as Biological Response Modifier in Cancer Patients. Anticancer Res. Mar-Apr 18 (2B), 1329–32. PMID: 9615811
Duque, G. A., Descoteaux, A. (2014). Macrophage Cytokines: Involvement in Immunity and Infectious Diseases. Front Immunol. 5, 491. doi: 10.3389/fimmu.2014.00491
Beutler, B. A. (1994). The role of tumor necrosis factor in health and disease. J Rheumatol Suppl (1999) 57. 16–21.
Camila, K., Janniger, et al. (2019). What is the mortality rate for herpes zoster (shingles)? S.C. Jan 25. https://www.medscape.com/answers/1132465-40968/what-is-the-mortality-rate-for-herpes-zoster-shingles
Miller, S. R., Pandi-Perumal, A. I., Esquifino, D. P., Cardinali, G. J. M. Maestroni. (2006). The role of melatonin in immuno-enhancement: potential application in cancer. Int. Medscape. J. Exp. Pathol. 87, 81–87, https://doi.org/10.1111/j.0959-9673.2006. 00474.x
Kaur, C., Ling, E. A. (1999). Effects of melatonin on macrophages/microglia in postnatal rat brain. J. Pineal Res. 26, 158–168 https://doi.org/10.1111/j.1600-079x. 1999.tb00578.x
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