Skip to main content
SpringerLink
Log in

Estimation of mRNA levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-4 and interferon (IFN)-γ in HIV infected children in Mumbai

  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Cytokines, viral load and opportunistic infections play an important role in HIV-disease progression. Hundred children vertically infected with HIV were enrolled to determine mRNA levels of TNF-α, IL-10, IL-4 and IFN-γ. These levels were estimated by amplifying cytokine mRNA from peripheral blood mononuclear cells. Severity of HIV was staged by the reduction in CD4 + T cells and the onset of opportunistic infections. IL-10 mRNA levels were observed to increase with the severity. Despite the rising IL-10 mRNA levels, TNF-α mRNA levels increased with severity of HIV and decrease in CD4 + T cell counts. IL-4 mRNA levels increased with the reduction in CD4 + T cell numbers. Depleting mRNA levels of IFN-γ contributed to the worsening of HIV disease. Increase in TNF-α and IL-4 levels appended to the disease severity by upregulation of the viral replication. Increased IL-10 levels and decreased IFN-γ levels predisposed the children to HIV associated opportunistic infections, which in return contributed to cytokine disarray.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gutman, L. T., St Claire, K. K. and Weedy, C. (1991) Human Immunodeficiency Virus transmission by child sexual abuse. Am. J. Dis. Child. 145, 137.

    PubMed  CAS  Google Scholar 

  2. Cohen, J. (2004). Till death do us part. Science 304, 513.

    Article  PubMed  CAS  Google Scholar 

  3. UNAIDS/WHO (2004). Joint United Nations Programme on HIV/AIDS (UNAIDS), World Health Organization (WHO), UNAIDS/04.45E. December 2004).

  4. <http://www.naco.nic.in/indianscene/overv.htm,04/06/04>

  5. Fiorentino, D., Bond, M. and Mossmann, T. (1989). Two types of mouse T helper cells IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J. Exp. Med. 170, 2081.

    Article  PubMed  CAS  Google Scholar 

  6. Wierenga, E.A., Snoek, M., de Groot, C., Chretien, I., Bos, J.D., Jansen, H.M. and Kapenberg, M.L. (1990) Evidence for compartmentalization of functional subsets of CD4 + T lymphocytes in atopic patients. J. Immunol. 144, 4651.

    PubMed  CAS  Google Scholar 

  7. Manetti, R., Parronchi, P., Giudizi, M., Piccinni, M., Maggi, E., Tinchieri, G. and Romagnani, S. (1993) Natural killer cell stimulatory factor (IL-12) induces T helper type 1 (Th1) specific immune responses and inhibits the development of IL-4 producing Th cells. J. Exp. Med. 177, 1199.

    Article  PubMed  CAS  Google Scholar 

  8. Clerici, M. and Shearer, G. M. (1993) A Th1 to Th2 shift is a critical step in the etiology of HIV infection. Immunol. Today 14, 107.

    Article  PubMed  CAS  Google Scholar 

  9. MacDonell, K.B., Chimiel, J.S., Poggensee, L., Wu, S. and Phair, J.P. (1990) Predicting progression to AIDS: combined usefulness of CD4 lymphocyte counts and p24 antigenemia. Am. Med. Journal 89, 706.

    Article  CAS  Google Scholar 

  10. Thomson, A.W. (ed.) (1998). The Cytokine Handbook, 3rd edition, Academic Press Ltd., San Diego, CA, 491.

    Google Scholar 

  11. Gajewski, T.F., Joyce, J. and Fitch, F.W. (1990) Anti-proliferative effect of IFN-γ in immune regulation. J. Immunol. 143, 15.

    Google Scholar 

  12. Schindler, H., Lutz, M.B., Rollinghoff, M. and Bogdan, C. (2001). The production of IFN-γ by IL-12/IL-18 activated macrophages requires STAT4 signaling and is inhibited by IL-4. J. Immunol. 166, 3075.

    PubMed  CAS  Google Scholar 

  13. Noble, A. and Kemeny, D.M. (1995). IL-4 enhances IFN-γ synthesis bu tinhibits the development of IFN-γ producing cells. Immunol. 85, 357.

    CAS  Google Scholar 

  14. de Waal Malefyt, R., Abrams, J., Bennet, B., Figdor, G. and de Vries, J.E., (1991) IL-10 inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J. Exp. Med. 174, 1209.

    Article  PubMed  Google Scholar 

  15. Lonnemann, G., Endres, C.A., Van der Meer, J.W.M., Cannon, J.G., Koch, K.M. and Dinarello, C.A. (1989). Differences in the synthesis and kinetics of release of Interleukin 1a, Interleukin 1b and tumor necrosis factor from human mononuclear cells. Eur. J. Immunol. 19, 1531.

    Article  PubMed  CAS  Google Scholar 

  16. Airoldi, I., Saverino, D. and Favre, A. (2000). Cytokine gene expression and T-cell proliferative responses in lymph node mononuclear cells from children with early stage human immunodeficiency virus infection. Hematologica 85, 1237.

    CAS  Google Scholar 

  17. Khilnani, P., Rajdev, S.K. and Uttam, R. (2003). Pediatric AIDS: Part-1. Ind. J. Crit. Care Med. 7 (4), 257.

    Google Scholar 

  18. Madhivanan, P., Mothi, S.N. and Kumarasamy, N. (2003). Clinical manifestations of HIV infected children. Ind. J. Pediatr. 70, 615.

    Article  Google Scholar 

  19. www.unaids.org, 03/12/01.

  20. Navikas, V., Link, J. and Persson, C. (1995). Increased mRNA expression of IL-6, IL-10, TNF-α and Perforin in Blood Mononuclear Cells in Human HIV infection. J. AIDS and Human Retrovirology 484.

  21. Chehimi, J., Xiaojing, M. and Chouaib, S. (1996). Differential production of interleukin 10 during human immunodeficiency virus infection. AIDS Res. Hum. Retro. 12 (12), 1141.

    CAS  Google Scholar 

  22. Clerici, M., Balotta, C., Meroni, L. and Ferrario, E. (1996) Type 1 cytokine production and low prevalence of viral isolation correlate with long-term non-progression in HIV infection. AIDS Res. Hum. Retro. 12 (11), 1053.

    CAS  Google Scholar 

  23. Alimonti, J.B., Ball, T.B. and Fowke, K.R. (2003) Mechanisms of CD4 + T lymphocyte cell death in Human Immunodeficiency Virus infection and AIDS. J. Gen. Virol. 84 (7), 1649.

    Article  PubMed  CAS  Google Scholar 

  24. Than, S., Hu, R. and Oyaizu, N. (1997). Cytokine pattern in relation to disease progression in human immunodeficiency virus-infected children. J. Infect. Dis. 175 (1), 47.

    PubMed  CAS  Google Scholar 

  25. De S.K., Devadas, K. and Notkins, A.L. (2002). Elevated levels of tumor necrosis factor alpha (TNF-α) in Human Immunodeficiency Virus type 1 transgenic mice: Prevention of death by antibody to TNF-α. J. Virol. 76 (22), 11710.

    Article  PubMed  CAS  Google Scholar 

  26. Bajaj, J.S., Singh, A., Aggarwal, S.K., Chattopadhya, D. and Baveja, U.K. (2002) Synergistic immunosuppression by candida in HIV infection: a cytokine based analysis. J. Commun. Dis. 32 (1), 1.

    Google Scholar 

  27. van Crevel, R., Karyadi, E., Preyers, F. and Leenders, M. (2000). Increased production of interleukin 4 by CD4 + and CD8 + T cells from patients with tuberculosis is related to the presence of pulmonary cavities. J. Infect. Dis. 187 (3), 1194.

    Article  Google Scholar 

  28. Maggi, E., Mazzetti, M. and Romagnani, S. (1994). Ability of HIV to promote a Th1 to Th2 shift and to replicate preferentially in Th2 and Th0 cells. Science 265, 244.

    Article  PubMed  CAS  Google Scholar 

  29. Kazazi, F., Mathijs, J. and Chang J. (1992). Recombinant interleukin 4 stimulates human immunodeficiency virus production by infected monocytes and macrophages. J. Gen. Virol. 73, 941.

    Article  PubMed  CAS  Google Scholar 

  30. Meyaard, L., Otto, S.A., Keet, I.P., van Lier, R.A. and Miedema, F. (1994). Changes in cytokine secretion pattern of CD4 + T clones in Human Immunodeficiency Virus infection. Blood 84 (12), 4262.

    PubMed  CAS  Google Scholar 

  31. Gong, J., Zhang, M. and Modlin, R. (1996). Interleukin-10 downregulatesMycobacterium tuberculosis-induced Th1 responses and CTLA-4 expression. Nutrition and Immunity 913.

  32. Uittenbogaart, C.H., Anisman, D.J. and Jack, J.A. (1994). Effects of cytokines on HIV-1 production by thymocytes. Thymus 23 (34), 155.

    PubMed  CAS  Google Scholar 

  33. Bailer, R., Holloway, A. and Sun J. (1999). IL-13 and IFN-γ secretion by activated T cells in HIV-1 infection associated with viral suppression and a lack of disease progression. J. Immunol. 162 (12), 7534.

    PubMed  CAS  Google Scholar 

  34. Atfeld, M., Addo, M. and Kreuzer, K. (2000) Th1 to Th2 shift of cytokines in peripheral blood of HIV-infected patients is detectable by reverse transcriptase Polymerase Chain Reaction but not by Enzyme-Linked Immunosorbent Assay under Nonstimulated conditions. J. AIDS 23 (4), 287.

    Google Scholar 

  35. Tanaka, M., Hirabayashi, Y. and Gatanaga, H. (1999). 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. 50 (5), 550.

    Article  PubMed  CAS  Google Scholar 

  36. Meuller, Brigitta, Pizzo, Philip, (1997). Pediatric Human Immunodeficiency Virus Infections, In AIDS: Etiology, Diagnosis, Treatment and Prevention, 4th edition, ed. DeVita Jr. V., Hellman S., Rosenberg, S. 443–464.

    Google Scholar 

  37. Gordon, S. (2003). Alternative activation of macrophages. Nat. Rev. Immunol. 3 (1), 23–35.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Virology, Haffkine Institute for Training, Research and Testing, A. D. Marg, Parel, 12, Mumbai

    Sweta T. Kothari & Ranjana A. Deshmukh

Authors
  1. Sweta T. Kothari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ranjana A. Deshmukh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kothari, S.T., Deshmukh, R.A. Estimation of mRNA levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-4 and interferon (IFN)-γ in HIV infected children in Mumbai. Indian J Clin Biochem 21, 15–26 (2006). https://doi.org/10.1007/BF02913062

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02913062

Keywords

Search

Navigation