COMPARATIVE CHARACTERISTICS OF CYTOKINE PROFILES IN PATIENTS WITH ACUTE CONDYLOMAS OF THE ANOGENITAL REGION UNDERGOING SURGICAL TREATMENT WITH ELECTROCOAGULATION AND MEDICAL LASER WHILE USING THE NITROGEN DONOR ARGININE ASPARTATE
DOI:
https://doi.org/10.11603/1811-2471.2025.v.i4.15785Keywords:
genital warts, Buschke-Levenstein condylomas, electrocoagulation, surgical laser, cytokine profile, NO donorAbstract
SUMMARY. The aim – to study the effect of arginine aspartate on cytokine dynamics in patients with genital warts in the postoperative period using electrocoagulation and medical laser.
Material and Methods. 146 patients with acute condylomas of the anogenital region were examined and treated, and divided into three groups. Group 1 (n=70): patients with multiple ACAR’s– 47 (67.14 %); single – 21 (30.0 %); Buschke-Levenshtein condylomas – 2 (2.86 %). Group 2 (n=35): multiple – 19 (54.29 %); single – 15 (42.86 %); Buschke-Levenstein condylomas – 1 (2.86 %). Group 3 (n=41): multiple – 21 (51.22 %); solitary – 20 (48.78 %). All patients received local therapy with a preparation consisting of the antiseptic Decamethoxin and sodium hyaluronate, as well as systemic therapy with the immunomodulator Aloferon. Patients in groups 1 and 3 received NO donor for 10 days in the preoperative period and 10 days after surgery. Destruction of genital warts in groups 1 and 2 was performed by electrocoagulation. In group 3, a surgical laser was used in scalpel or vaporization mode. Cytokine levels (IL-4, 6, 8, TNF-α) were determined at the beginning of preoperative preparation and on the 10th day of the postoperative period.
Results. During the initial study of the cytokine profile in patients, we found a significant increase in the levels of proinflammatory interleukins IL-6, IL-8, anti-inflammatory IL-4, and tumor necrosis factor (TNF-a), characterized by a 3.5-fold increase in TNFa levels, a 2.5-fold increase in IL-6 levels, IL-8 – 1.8; and anti-inflammatory IL-4 – 2.5, relative to the control group (n = 20), with higher values in patients with a widespread process and giant Buschke-Levenstein condylomas. On the 10th day of the postoperative period in patients with multiple genital warts, TNF-a decreased by 2.6, 1.7 and 2.8 times, respectively, and did not differ significantly from the control values in groups 1 and 3. IL-6 decreased in all groups by 2.1, 1.63, and 2.5 times, respectively. The concentration of IL-8 decreased by 1.7, 1.6, and 1.8 times, respectively. The decrease in IL-4 relative to baseline values occurred in all groups by 1.85, 1.60, and 2.71 times, respectively. The positive dynamics of cytokines was more pronounced in group 3, when a surgical laser was used in combination with arginine aspartate.
In group 2, these indicators were significantly higher than in groups 1 and 3. This reflects the persistence of the inflammatory phase when using the electrocoagulation method. The more positive dynamics in group 1 compared to group 2 reflects the positive effect of arginine aspartate as an NO donor on the negative effects of the electrocoagulation method, which reduces the level of post-traumatic alteration.
In patients with isolated genital warts, no significant changes in the dynamics of the cytokine profile were observed.
Conclusions. In patients with genital warts, the level of proinflammatory cytokines depends on the spread of the process and the presence of secondary inflammation. In isolated forms of the disease, the level of cytokines does not differ significantly from the control group and does not show a clear tendency to change in the absence of complications in the postoperative period.
The dynamics of pro-inflammatory cytokine levels in comparison with the surgical destruction method shows the persistence of the inflammatory phase when using the electrocoagulation method.
Given the role of the endothelium in the wound healing process, the administration of NO donor drugs, which have a direct effect on the endothelium, leads to positive dynamics in the concentration of IL-4, IL-6, IL-8, TNF-a and neutralizes the persistence of the inflammatory phase of the wound healing process, which optimizes the course of the postoperative period.
References
Babenko NM. Features of the regulation of reparative processes of chronic wounds by cytokines using photobiomodulation therapy. Experimental and Clinical Physiology and Biochemistry. 2021;(3–4):5–10. DOI: https://doi.org/10.25040/ecpb2021.03-04.005
Volovar OS, Astapenko OO, Lytovchenko NM, Palyvoda RS. Wound healing and soft tissue regeneration: a literature review. Bukovynskyi Medical Herald. 2023; 27(3):101–104. DOI: 10.24061/2413-0737.27.3.107. 2023.17. DOI: https://doi.org/10.24061/2413-0737.27.3.107.2023.17
Glagolieva AY. Comparison of the effectiveness of prophylactic systemic administration of antibiotics with topical use of the antiseptic decamethoxin in clean surgical operations. Perioperative Medicine. 2019;2(2):8–13. DOI: 10.31636/prmd.v2i2.2. DOI: https://doi.org/10.31636/prmd.v2i12.2
Lych IV, Uhryn AO, Voloshyna IM. Hyaluronic acid: biosynthesis and use. Ukrainian Biopharmaceutical Journal. 2019;2(59):6–11. DOI: 10.24959/ubphj.19.212. DOI: https://doi.org/10.24959/ubphj.19.212
Mishchenko LA, Ovdiienko TM, Matova OO, Talaieva TV, Tretiak IV, Vasylinchuk NM, et al. Functional state of the endothelium and additional possibilities of its correction using ethylmethylhydroxypyridine succinate in patients with arterial hypertension. Ukrainian Medical Journal. 2021;4(144):2–5. DOI: 10.32471/umj.1680-3051. 144.213876. DOI: https://doi.org/10.32471/umj.1680-3051
Mohylnyk AI. Systemic capillary leak syndrome and methods of its correction in intensive therapy of critical conditions. Clinical Surgery. 2018;85(4):57–61. DOI: 10.26779/2522-1396.2018.04.57. DOI: https://doi.org/10.26779/2522-1396.2018.04.57
Nahaichuk VI, Nazarchuk OA, Chornopyshchuk RM, Harmash PP. Features of the wound process in the acute period of burn disease depending on the antibiotic used. Perioperative Medicine. 2019;2(2):14–23. DOI: 10.31636/ prmd.v2i2.3. DOI: https://doi.org/10.31636/prmd.v2i2.3
Nikitina NS, Stepanova LI, Vereshchaka VV, Savchuk OM, Beregova TV. Effect of carbopol gel with melanin on cytokine content in wound substrate of full-thickness skin wounds in rats. Bulletin of Problems of Biology and Medicine. 2019;1(150):168–171. DOI: 10.29254/ 2077-4214-2019-2-1-150-168-171. DOI: https://doi.org/10.29254/2077-4214-2019-2-1-150-168-171
Osinska TV. Prevalence of human papillomavirus among patients with sexually transmitted infections. Dermatology and Venereology. 2022;1–2:17–20. DOI: https://doi.org/10.33743/2308-1066-2022-1-2-17-20
Reheda MS, Boichuk TS, Bondarenko YI, Reheda MM. Inflammation – a typical pathological process. 2nd ed. Lviv: Lviv Medical Institute; 2013. 148 p.
Sokolenko MO, Moskaliuk VD, Sokolenko AA, Sorokhan VD, Boiko YI. Analysis of the effectiveness of Allokin-Alpha in complex therapy of recurrent herpes zoster. Infectious Diseases Journal. 2017;(1):22–27.
Sokolova LK, Pushkarev VM. The role of arginine in physiological processes in health and disease. Health of Ukraine. 2018 Jul 9:37–38.
Storozhenko OV, Lihonenko OV, Ivashchenko DM, Zubakha AB, Chorna IO, Shumeiko IA. Prediction of wound healing in patients allergic to antibiotics. Clinical Surgery. 2018;85(5):40–43. DOI: 10.26779/2522-1396. 2018.05.40. DOI: https://doi.org/10.26779/2522-1396.2018.05.40
Shcherbakova YV. Efficacy of imiquimod in the treatment of genital warts. Bulletin of the Ukrainian Medical Stomatological Academy. 2016;16(2):202–205.
Bacaj P, Burch D. Human papillomavirus infection of the skin. Arch Pathol Lab Med. 2018;142(6):700–705. DOI: 10.5858/arpa.2017-0572-RA. PMID:29848038. DOI: https://doi.org/10.5858/arpa.2017-0572-RA
Calik J, Zawada T, Bove T. Treatment of condylomata acuminata using a new non-vapor-generating focused ultrasound method following imiquimod 5 % cream. Case Reports in Dermatology. 2022;14(3):275–282. DOI: 10.1159/000525896. PMID:36824153. DOI: https://doi.org/10.1159/000525896
Clay PA, Thompson TD, Markowitz LE, Ekwueme DU, Saraiya M, Chesson HW. Updated estimate of annual direct medical cost of screening and treatment for HPV-associated disease in the United States. Vaccine. 2023;41(14):2376–2381. DOI: 10.1016/j.vaccine.2023.02.049. DOI: https://doi.org/10.1016/j.vaccine.2023.02.049
Egawa N, Doorbar J. The low-risk papillomaviruses. Virus Research. 2017;231:119–127. DOI:10.1016/j.virusres. 2016.12.017. DOI: https://doi.org/10.1016/j.virusres.2016.12.017
Freedberg IM, Tomic-Canic M, Komine M, Blumenberg M. Keratins and the keratinocyte activation cycle. J Invest Dermatol. 2001;116(5):633–640. DOI: 10.1046/ j.1523-1747.2001.01327.x. DOI: https://doi.org/10.1046/j.1523-1747.2001.01327.x
Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219–229. DOI: https://doi.org/10.1177/0022034509359125
Gutierrez P, Garza J, Gandhi K, Voice A, Stout E, Ventolini G. Carbon-dioxide (CO₂) laser ablation treatment of a periurethral genital wart. Case Reports in Women’s Health. 2020;27. Available from: www.elsevier.com/locate/crwh DOI: https://doi.org/10.1016/j.crwh.2020.e00226
Husseinzadeh N. Basic therapeutic principles and strategy in management of external anogenital warts (condylomas): a review. J Clin Gynecol Obstet. 2013;2(1):1–9. DOI: https://doi.org/10.4021/jcgo86e
Yuan J, Ni G, Wang T, Mounsey K, Cavezza S, Pan X, Liu X. Genital warts treatment: beyond imiquimod. Hum Vaccin Immunother. 2018;14(7):1815–1819. DOI: 10.1080/ 21645515.2018.1445947. DOI: https://doi.org/10.1080/21645515.2018.1445947
Leslie SW, Sajjad H, Kumar S. Genital warts. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441884
Nie W, Liu Y, Lan J, Li T, He Y, Li Z, et al. Self-assembled nanoparticles from Xie-Bai-San decoction: isolation, characterization and enhancing oral bioavailability. Int J Nanomedicine. 2024;19:3405–3421. DOI: 10.2147/IJN.S449268. DOI: https://doi.org/10.2147/IJN.S449268
Niu L, Chu X, Jiang Y, Zeng W. HPV infection upregulates the expression of ZNT-1 in condyloma acuminatum. Eur J Histochem. 2021;65(2):3228. DOI: 10. 4081/ejh.2021.3228. DOI: https://doi.org/10.4081/ejh.2021.3228
Özkaya DB, Erfan G, Çıtamak B. The effectiveness of genital wart treatments. J Urol Surg. 2023;10(3):179–188. DOI: 10.4274/jus.galenos.2023.2023-6-8. DOI: https://doi.org/10.4274/jus.galenos.2023.2023-6-8
Pavlov SB, Tamm TI, Komisova TYe, Babenko NM, Kumechko MV, Litvinova OB. The nature of changes in endocrine and immune factors at the initial stage of chronic wound formation. Modern Medical Technologies. 2023;2(57):34–39. DOI: https://doi.org/10.34287/MMT.2(57).2023.6
Scheifeld N. Update on the treatment of genital warts. Dermatology Online Journal. 2013;19(3). DOI: 10. 5070/D3196018559. Available from: https://escholarship.org/uc/item/42v5g88
Slowik M, Gierlach K, Nowak K, Drygała Z, Zielińska Z, Wyrwał J, et al. The condyloma acuminata—review of treatment methods. J Educ Health Sport. 2024;59:31–45. DOI:10.12775/JEHS.2024.59.002. DOI: https://doi.org/10.12775/JEHS.2024.59.002
Stuqui B, Provazzi PJS, Lima MLD, Cabral ÁS, Leonel ECR, Candido NM, et al. Condyloma acuminata: an evaluation of the immune response at cellular and molecular levels. PLoS One. 2023;18(4):e0284296. DOI: 10.1371/journal.pone.0284296. DOI: https://doi.org/10.1371/journal.pone.0284296
Veasey JV, Campaner AB, Lellis RF. Aspects of Langerhans cells and TNF-alpha in the cutaneous immunity of anogenital warts. An Bras Dermatol. 2020;95(2):144–149. PMID:32146009. DOI: https://doi.org/10.1016/j.abd.2019.06.007
Velnar T, Gradisnik L. Tissue augmentation in wound healing: the role of endothelial and epithelial cells. Med Arch. 2018;72(6):444–448. DOI: 10.5455/medarh. 2018.72.444-448. PMID:30814778; PMCID:PMC6340622. DOI: https://doi.org/10.5455/medarh.2018.72.444-448
Zhang D, Qu Y, Sui C, Li M, Yuan Y, Wang N, Ma W. CD-207 expression level is a new prognostic marker for condyloma acuminatum. Clin Cosmet Investig Dermatol. 2023;16:1607–1613. DOI:10.2147/CCID.S412162. DOI: https://doi.org/10.2147/CCID.S412162
Zhou P, Feng H, Qin W, Li Q. KRT-17 from skin cells under high-glucose stimulation promotes keratinocyte proliferation and migration. Front Endocrinol (Lausanne). 2023;14:1237048. DOI:10.3389/fendo.2023.1237048. DOI: https://doi.org/10.3389/fendo.2023.1237048
