Document Type : Original Research


1 Payame Noor University, Arak, Iran

2 Dept. of Clinical Research, Pasteur Institute of Iran, Tehran, Iran

3 Iranian Research Center for HIV/AIDS, Tehran, Iran

4 Iranian Society for Support of Patients with Infectious Diseases, Tehran, Iran

5 Alzahra University, Tehran, Iran


Background and Objectives: Infection with human immunodeficiency virus (HIV) results in dysregulation of the cytokine profile. A switch from a T helper 1 (Th1) to a Th2 cytokine has been proposed as an important factor in progression of HIV infection to AIDS. The aim of the present study was to assess the level of Th1 and Th2 cytokines in HIV infected individuals in order to identify the switch from Th1 to Th2 cytokines.
Materials and Methods: This study was carried out on 140 HIV infected patients (21 treatment naïve and 119 under treatment) and 35 matched healthy controls refereed to Iranian Research Center for HIV/AIDS, Tehran, Iran. The serum samples were checked with enzyme-linked immunosorbent assay (ELISA) for interleukin (IL)-2, IL-4, IL-10 and interferon (IFN)-gamma. The Chi-square and t2-tests were used with the SPSS 16 package program for statistical analysis
Results: A total of 140 HIV positive patients with mean age 36.9±9.2 years and 35 matched controls were enrolled in the study. IL-2 level was relatively higher and IL-10, IL-4 and IFN-gamma levels were relatively lower in the treatment naïve group than the under treatment group. Except for IL-2, all of the other cytokines exhibited a negative correlation with the CD4 cell counts and IFN-gamma levels showed the strongest negative correlation.
Conclusion: Our observations did not demonstrate switching of the type 1 to type 2 T helper cells cytokine profile in HIV infected patients and suggested more complex changes in Th1 to Th2 cytokine patterns in HIV infection.


  1. Clerici M, Shearer GM. The Th1-Th2 hypothesis of HIV infection: new insights. Immunol Today 1994; 15:575–81.
  2. Watanabe D, Uehira T, Yonemoto H, Bando H, Ogawa Y, Yajima K, et al. Sustained high levels of serum interferon-γ during HIV-1 infection: a specific trend different from other cytokines. Viral Immunol 2010;23(6):619-25.
  3. Iannello A, Boulassel MR, Samarani S, Debbeche O, Tremblay C, Toma E, et al. Dynamics and consequences of IL-21 production in HIV-infected individuals: a longitudinal and cross-sectional study. J Immunol 2010;184(1):114-26.
  4. Shearer GM. HIV-induced immunopathogenesis. Immunity 1998;9(5):587-93.
  5. Sirskyj D, Thèze J, Kumar A, Kryworuchko M. Disruption of the gamma c cytokine network in T cells during HIV infection. Cytokine 2008;43(1):1-14.
  6. Pahwa S. Role of common gamma chain utilizing cytokines for immune reconstitution in HIV infection. Immunol Res 2007; 38(1-3):373-86.
  7. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, Markowitz M, et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J Exp Med 2001;194:1277–87.
  8. Guadalupe M, Reay E, Sankaran S, Prindiville T, Flamm J, McNeil A,  et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77:11708–17.
  9. Pantaleo G, Graziosi C, Fauci AS. The role of lymphoid organs in the pathogenesis of HIV infection. Semin Immunol 1993;5(3):157-63.
  10. Lucey DR, Clerici M, Shearer GM. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 1996;9:532–62.
  11. Scott-Algara D, Vuillier F, Marasescu M, de Saint Martin J, Dighiero G. Serum levels of IL-2, IL-1 alpha, TNF-alpha,and soluble receptor of IL-2 in HIV-1-infected patients. AIDS Res Hum Retroviruses 1991;7:381–86.
  12. Breen EC, Rezai AR, Nakajima K, Beall GN, Mitsuyasu RT, Hirano T, et al. Infection with HIV is associated with elevated IL-6 levels and production. J Immunol 1990; 144:480–484.
  13. Ameglio, F., Cordiali Fei P, Solmone M, Bonifati C, Prignano G, Giglio A, et al. Serum IL-10 levels in HIV-positive subjects: correlation with CDC stages. J Biol Regul Homeost Agents 1994;8:48–52.
  14. Alonso K, Pontiggia P, Medenica R, and Rizzo S. Cytokine patterns in adults with AIDS. Immunol Invest 1997;26:341–50.
  15. Fakoya A, Matear PM, Filley E, Rook GA, Stanford J, Gilson RJ, et al. HIV infection alters the production of both type 1 and 2 cytokines but does not  induce a polarized type 1 or 2 state. AIDS 1997;11:1445–52.
  16.  Graziosi C, Pantaleo G, Gantt KR, Fortin JP, Demarest JF, Cohen OJ, et al. Lack of evidence for the dichotomy of TH1 and TH2 predominance in HIV-infected individuals. Science 1994;265:248–52.
  17.  Tanaka M, Hirabayashi Y, Gatanaga H, Aizawa S, Hachiya A, Takahashi Y, et al. Reduction in interleukin-2-producing cells but not Th1 to Th2 shift in moderate and advanced stages of human immunodeficiency virus type-1-infection: direct analysis of intracellular cytokine concentrations in CD4+CD8_ T cells. Scand J Immunol 1999;50:550–4.
  18. Aziz N, Nishanian P, Fahey JL. Levels of cytokines and immune activation markers in plasma in human immunodeficiency virus infection: quality control procedures. Clin Diagn Lab Immunol 1998;5:755–61.
  19. Orsilles MA, Pieri E, Cooke P, Caula C. IL-2 and IL-10 serum levels in HIV-1-infected patients with or without active antiretroviral therapy. APMIS 2006; 114:55–60.
  20. Stylianou E, Bjerkeli V, Yndestad A, Heggelund L, Waehre T, Damås JK, et al. Raised serum levels of interleukin-18 is associated with disease progression and may contribute to virological treatment failure in HIV-1-infected patients. Clin Exp Immunol 2003;132:462–466.
  21. Llano A, Barretina J, Gutierrez A, Blanco J, Cabrera C, Clotet B, Este JA. Interleukin-7 in plasma correlates with CD4 T-cell depletion and may be associated with emergence of syncytium-inducing variants in human immunodeficiency virus type 1-positive individuals. J Virol 2001;75:10319–25.
  22. Norris S, Collins C, Doherty DG, Smith F, McEntee G, Traynor O, et al. Resident human hepatic lymphocytes are phenotypically different from circulating lymphocytes. J Hepatol 1998;28:84–90.
  23. Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother 2001; 12(3):133-50.
  24. Clerici M, Hakim FT, Venzon DJ, Blatt S, Hendrix CW, Wynn TA, et al. Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals. J Clin Invest 1993; 91:759–65.
  25. Becker Y. The changes in the T helper 1 (Th1) and T helper 2 (Th2) cytokine balance during HIV-1 infection are indicative of an allergic response to viral proteins that may be reversed by Th2 cytokine inhibitors and immune response modifiers—a review and hypothesis. Virus Genes 2004;28:5–18.
  26. Notermans DW, Jurriaans S, de Wolf F, Foudraine NA, de Jong JJ, Cavert W, et al. Decrease of HIV-1 RNA levels in lymphoid tissue and peripheral blood during treatment with ritonavir, lamivudine and zidovudine. Ritonavir/3TC/ZDV Study Group. AIDS 1998;12:167–73.
  27. Westby M, Marriott JB, Guckian M, Cookson S, Hay P, Dalgleish AG. Abnormal intracellular IL-2 and interferon-gamma (IFN-g) production as HIV-1-associated markers of immune dysfunction. Clin Exp Immunol 1998;111:257–63.
  28. Klein SA, Dobmeyer JM, Dobmeyer TS, Pape M, Ottmann OG, Helm EB, et al. Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry. AIDS. 1997; 11(9):1111-8.