DYNAMICS OF IL-2 PLASMA LEVELS IN HIV PATIENTS WITH CONSIDERING DRUGS RESISTANCE

Cover Page


Cite item

Full Text

Abstract

Interleukin-2 (IL-2) is one of the most important cytokines involved in the regulation of innate and adaptive immunity. Its main  immunological function is to regulate a specific (antigen-dependent)  immune response by stimulating proliferation and differentiation of  immune cells involved in its realization, including Т-lymphocytes.  Dysfunction of cellular immunity is the main pathogenetic  mechanism for the development of HIV infection.

Objective: to  identify patterns of IL-2 levels change in HIV-infected patients on the background of drug resistance at the later stages of infection. The study included 83 patients with HIV infection receiving  highly active antiretroviral therapy; the control group  consisted of 20 healthy blood donors. All patients underwent a study  of the effectiveness of antiretroviral therapy, including an  assessment of HIV viral load and CD4+ Т lymphocyte levels. In  patients with ineffective antiretroviral therapy, a study of drug  resistance to HIV by Senger sequencing was additionally conducted.  According to the results of genome sequencing, HIV-infected  patients with ineffective antiretroviral therapy were divided into two  subgroups — with revealed drug resistance (58.5%) and absence of  detectable resistance mutations in the genome (41.5%). Levels of  IL-2 were measured in all persons included in the study by the  method of enzyme immunoassay. When comparing the levels of IL-2 between groups of patients with continuing viral load on the background of antiretroviral therapy (viral load is detected) with  drug resistance and without it, significant differences were obtained  (1.75±0.26 pg/ml versus 1.95±0.29 pg/ml, p ≤ 0.05, U-criterion,  respectively). The content of IL-2 is statistically significantly lower in  the group of patients who did not succeed with antiretroviral therapy than in the group of patients with treatment efficacy (1.83±0.29 pg/ml versus 4.89±0.55 pg/ml, respectively, p < 0.001, U-criterion). Thus, it is shown that in patients with revealed drug resistance  against the background of progression of HIV infection there is a  decrease in levels of IL-2. The increase in its levels in patients with  HIV infection who have reached virological and immunological  success of therapy is due to the reduction in the number of the cytokine-producing immune cells (T-lymphocytes). We assume that a significant decrease in the levels of IL-2 makes an additional  contribution to the disruption of the processes of proliferation and  differentiation of immunocompetent cells in HIV infection, which is of great importance in the formation of drug resistance of HIV in conditions of constant viral replication.

About the authors

E. S. Eliseeva

Center for prevention and control of AIDS and infectious diseases

Author for correspondence.
Email: vic-eliseeva@mail.ru

Doctor of Laboratory Diagnostics, Clinical and Immunological  Laboratory, Regional Clinical Hospital No. 2, Center for  Prevention and Control of AIDS and Infectious Diseases, Vladivostok, Russian Federation

690011, Russian Federation, Vladivostok, Borisenko str., 50

Phone: +7 (423) 263-62-24 (office)

Russian Federation

S. P. Kruglak

Center for prevention and control of AIDS and infectious diseases

Email: fake@neicon.ru

PhD (Medicine), Head of the Clinical and Immunological  Laboratory, Regional Clinical Hospital No. 2, Center for  Prevention and Control of AIDS and Infectious Diseases, Vladivostok, Russian Federation

Russian Federation

L. F. Sklar

Center for prevention and control of AIDS and infectious diseases

Email: fake@neicon.ru

PhD, MD (Medicine), Professor, Department of Infectious Diseases, Pacific State Medical University,  Vladivostok, Russian Federation; Deputy Chief Doctor of the  Center for Prevention and Control of AIDS and Infectious Diseases, Vladivostok, Russian Federation

Russian Federation

E. V. Markelova

Pacific State Medical Univercity

Email: fake@neicon.ru

PhD, MD (Medicine), Professor, Department of Normal and  Pathological Physiology, Pacific State Medical University, Vladivostok, Russian Federation

Russian Federation

N. A. Borovskaya

Pacific State Medical Univercity

Email: fake@neicon.ru

PhD (Medicine), Associate Professor, Department of Infectious  Diseases, Pacific State Medical University, Vladivostok, Russian Federation

Russian Federation

References

  1. Агошков А.А., Пшеничная Н.Ю., Айдамирова Х.А., Шевченко Т.А. Клинико-лабораторные и эпидемиологические аспекты ВИЧ-инфекции в «продвинутых» стадиях в Чеченской Республике // Цитокины и воспаление. 2014. Т. 13, № 3. С. 70–71. [Agoshkov A.A., Pshenichnaya N.Y., Aidamirova H.A., Shevchenko T.A. Clinical, laboratory and epidemiological aspects of HIV-infection in the late stages in the Chechen Republic. Tsitokiny i vospalenie = Cytokines and Inflammation, 2014, vol. 13, no. 3, pp. 70–71. (In Russ.)]
  2. Бобкова М.Р. Лекарственная устойчивость ВИЧ. М.: Человек, 2014. 288 с. [Bobkova M.R. Lekarstvennaya ustoichivost’ VICh [HIV drug resistance]. Moscow: Chelovek, 2014. 288 p.]
  3. Вирус иммунодефицита человека – медицина. Под ред. Белякова Н.А., Рахмановой А.Г. СПб.: Балтийский медицинский образовательный центр, 2010. 752 с. [Virus immunodefitsita cheloveka — meditsina. Pod red. Belyakova N.A., Rakhmanovoi A.G. [Human immunodeficiency virus — medicine. Eds. Belyakov N.A., Rakhmanova A.G.]. St. Petersburg: Baltiiskii Meditsinskii Obrazovatel’nyi Tsentr, 2010. 752 p.]
  4. Гашникова Н.М., Богачев В.В., Барышев П.Б., Мещерякова Ю.В., Савочкина Е.Н., Черноусова Н.Я. Распространенность мутаций, ответственных за резистентность к антиретровирусным препаратам, среди вариантов ВИЧ-1, циркулирующих в Новосибирской области // Журнал микробиологии, эпидемиологии и иммунобиологии. 2012. № 6. С. 56–60. [Gashnikova N.M., Bogachev V.V., Baryshev P.B., Mescheryakova Yu.V., Savochkina E.N., Chernousova N.Ya. Prevalence of mutations responsible for resistance to antiretroviral preparations among HIV-1 variants circulating in Novosibirsk region. Zhurnal mikrobiologii, epidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology, 2012, no. 6, pp. 56–60. (In Russ.)]
  5. Покровский В.В., Юрин О.Г., Кравченко А.В., Беляева В.В., Канестри В.Г., Афонина Л.Ю., Ермак Т.Н., Буравцова Е.В., Шахгильдян В.И., Козырина Н.В., Нарсия Р.С., Зимина В.Н., Покровская А.В., Ефремова О.С. Протоколы диспансерного наблюдения и лечения больных ВИЧ-инфекцией // Эпидемиология и инфекционные болезни. Актуальные вопросы. 2014. № 6. С. 1–43. [Pokrovskiy V.V., Yurin O.G., Kravchenko A.V., Belyaeva V.V., Kanestri V.G., Afonina L.Yu., Ermak T.N., Buravcova E.V., Shakhgildyan V.I., Kozirina N.V., Narsia R.S., Zimina B.N., Pokrovskaya A.V., Efremova O.S. Protocols dispensary observation and treatment of patients with HIV-infection. Epidemiologiya i infektsionnye bolezni. Aktual’nye voprosy = Epidemiology and Infectious Diseases. Current Items, 2014, no. 6, pp. 1–43. (In Russ.)]
  6. Селимова Л.М., Серебровская Л.В., Иванова Л.А., Носик Д.Н. Показатели CD4+ и CD8+ Т-лимфоцитов пациентов, инфицированных вариантами вируса иммунодефицита человека 1-го типа подтипа А, несущими мутации V77I в протеазе и A62V в обратной транскриптазе // Вопросы вирусологии. 2010. № 2. С. 22–26. [Selimova L.M., Serebrovskaya L.V., Ivanova L.A., Nosik D.N. CD4+ and CD8+ T-lymphocyte counts in human immunodeficiency virus type 1 subtype A-infected patients carrying mutations V77I in protease and/or A62V in reverse transcriptase. Voprosy virusologii = Problems of Virology, 2010, no. 2, pp. 22–26. (In Russ.)]
  7. Симбирцев А.С. Цитокины в патогенезе инфекционных и неинфекционных заболевании человека // Медицинский академический журнал. 2013. Т. 13, № 3. С. 18– 41. [Simbirtsev A.S. Cytokines in the pathogenesis of infectious and noninfectious human diseases. Meditsinskii akademicheskii zhurnal = Medical Aсademical Journal, 2013, vol. 13, no. 3, pp. 18–41. (In Russ.)]
  8. Хоффман К., Рокштро Ю.К. Лечение ВИЧ-инфекции. М.: Р. Валент, 2012. 736 с. [Hoffman K., Rockstroh Yu.K. Lechenie VICh-infekcii [Treatment of HIV infection]. Moscow: R. Valent, 2012, 736 р.]
  9. Шипилов М.В. Интерлейкин-2 и острые респираторные вирусные инфекции // Известия Смоленского государственного университета. 2011. № 3. С. 294–299. [Shipilov M.V. Interleukin-2 and acute respiratory viral infections. Izvestija Smolenskogo gosudarstvennogo universiteta = Smolensk State University News, 2011, no. 3, pp. 294–299. (In Russ.)]
  10. Armah K.A., McGinnis K., Baker J., Gibert C., Butt A.A., Bryant K.J., Goetz M., Tracy R., Oursler K.K., Rimland D., Crothers K., Rodriguez-Barradas M., Crystal S., Gordon A., Kraemer K., Brown S., Gerschenson M., Leaf D.A., Deeks S.G., Rinaldo C., Kuller L.H., Justice A., Freiberg M. HIV status, burden of comorbid disease, and biomarkers of inflammation, altered coagulation, and monocyte activation. Clin. Infect. Dis., 2012, vol. 55, no. 1, pp. 126– 136. doi: 10.1093/cid/cis406
  11. Bebell L.M., Passmore J.A., Williamson C., Mlisana K., Iriogbe I., van Loggerenberg F., Karim Q.A., Karim S.A. Relationship between levels of inflammatory cytokines in the genital tract and CD4+ cell counts in women with acute HIV-1 infection. J. Infect. Dis., 2008, vol. 198, iss. 5, pp. 710–714. doi: 10.1086/590503
  12. Cellerai C., Harari A., Stauss H., Yerly S., Geretti A.M., Carroll A., Yee T., Ainsworth J., Williams I., Sweeney J., Freedman A., Johnson M., Pantaleo G., Kinloch-de Loes S. Early and prolonged antiretroviral therapy is associated with an HIV-1specific T-cell profile comparable to that of long-term non-progressors. PloS ONE, 2011, vol. 6, iss. 4: e18164. doi: 10.1371/journal.pone.0018164
  13. David D., Keller H., Naït-Ighil L., Treilhou M.P., Joussemet M., Dupont B., Gachot B., Maral J., Thèze J. Involvement of Bcl-2 and IL-2R in HIV-positive patients whose CD4 cell counts fail to increase rapidly with highly active antiretroviral therapy. AIDS, 2002, vol. 16, no. 8, pp. 1093–1101.
  14. Gaffen S.L., Liu K.D. Overview of interleukin-2 function, production and clinical applications. Cytokine, 2004, vol. 28, no. 3, pp. 109–123. doi: 10.1016/j.cyto.2004.06.010
  15. Gamberg J., Barrett L., Bowmer M.I., Howley C., Grant M. Factors related to loss of HIV-specific cytotoxic T lymphocyte activity. AIDS, 2004, vol. 18, no. 4, pp. 597–604.
  16. Haas A., Zimmermann K., Oxenius A. Antigen-dependent and -independent mechanisms of T and B cell hyperactivation during chronic HIV-1 infection. J. Virol., 2011, vol. 85, no. 23, pp. 12102–12103. doi: 10.1128/JVI.05607-11
  17. Mohri H., Perelson A.S., Tung K., Ribeiro R.M., Ramratnam B., Markowitz M., Kost R., Weinberger L., Cesar D., Hellerstein M.K., Ho D.D. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J. Exp. Med., 2001, vol. 194, no. 9, pp. 1277–1287. doi: 10.1084/jem.194.9.1277
  18. Norris P.J., Pappalardo B.L., Custer B., Spotts G., Hecht F.M., Busch M.P. Elevations in IL-10, TNF-α and IFN-γ from the earliest point of HIV type 1 infection. AIDS Res. Hum. Retrov., 2006, vol. 22, no. 8, pp. 757–762. doi: 10.1089/aid.2006.22.757
  19. Ostrowski S.R., Gerstoft J., Pedersen B.K., Ullum H. Impaired production of cytokines is an independent predictor of mortality in HIV-1-infected patients. AIDS, 2003, vol. 17, no. 4, pp. 521–530. doi: 10.1097/01.aids.0000050813.06065.ed
  20. Stacey A.R., Norris P.J., Qin L., Haygreen E.A., Taylor E., Heitman J., Lebedeva M., DeCamp A., Li D., Grove D., Self S.G., Borrow P. Induction of a striking systemic cytokine cascade prior to peak viraemia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J. Virol., 2009, vol. 83, no. 8, pp. 3719–3733. doi: 10.1128/JVI.01844-08
  21. Younes S.A., Yassine-Diab B., Dumont A.R., Boulassel M.R., Grossman Z., Routy J.P., Sekaly R.P. HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity. J. Exp. Med., 2003, vol. 198, no. 12, pp. 1909–1922. doi: 10.1084/jem.20031598

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2018 Eliseeva E.S., Kruglak S.P., Sklar L.F., Markelova E.V., Borovskaya N.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies