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. 2006 Mar;21(1):15–26. doi: 10.1007/BF02913062

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

Sweta T Kothari 1,✉, Ranjana A Deshmukh 1
PMCID: PMC3453749  PMID: 23105565

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.

Keywords: HIV, disease severity, mRNA levels, cytokines, children

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References

  • 1.Gutman L. T., St Claire K. K., Weedy C. Human Immunodeficiency Virus transmission by child sexual abuse. Am. J. Dis. Child. 1991;145:137–137. doi: 10.1001/archpedi.1991.02160020027008. [DOI] [PubMed] [Google Scholar]
  • 2.Cohen J. Till death do us part. Science. 2004;304:513–513. doi: 10.1126/science.304.5670.513. [DOI] [PubMed] [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., Mossmann T. Two types of mouse T helper cells IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J. Exp. Med. 1989;170:2081–2081. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Wierenga E.A., Snoek M., Groot C., Chretien I., Bos J.D., Jansen H.M., Kapenberg M.L. Evidence for compartmentalization of functional subsets of CD4+ T lymphocytes in atopic patients. J. Immunol. 1990;144:4651–4651. [PubMed] [Google Scholar]
  • 7.Manetti R., Parronchi P., Giudizi M., Piccinni M., Maggi E., Tinchieri G., Romagnani S. 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. 1993;177:1199–1199. doi: 10.1084/jem.177.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Clerici M., Shearer G. M. A Th1 to Th2 shift is a critical step in the etiology of HIV infection. Immunol. Today. 1993;14:107–107. doi: 10.1016/0167-5699(93)90208-3. [DOI] [PubMed] [Google Scholar]
  • 9.MacDonell K.B., Chimiel J.S., Poggensee L., Wu S., Phair J.P. Predicting progression to AIDS: combined usefulness of CD4 lymphocyte counts and p24 antigenemia. Am. Med. Journal. 1990;89:706–706. doi: 10.1016/0002-9343(90)90210-5. [DOI] [PubMed] [Google Scholar]
  • 10.Thomson A.W., editor. The Cytokine Handbook. 3rd edition. San Diego, CA: Academic Press Ltd.; 1998. pp. 491–491. [Google Scholar]
  • 11.Gajewski T.F., Joyce J., Fitch F.W.Anti-proliferative effect of IFN-γ in immune regulation J. Immunol. 199014315–15.2525146 [Google Scholar]
  • 12.Schindler H., Lutz M.B., Rollinghoff M., Bogdan C. The production of IFN-γ by IL-12/IL-18 activated macrophages requires STAT4 signaling and is inhibited by IL-4. J. Immunol. 2001;166:3075–3075. doi: 10.4049/jimmunol.166.5.3075. [DOI] [PubMed] [Google Scholar]
  • 13.Noble A., Kemeny D.M. IL-4 enhances IFN-γ synthesis bu tinhibits the development of IFN-γ producing cells. Immunol. 1995;85:357–357. [PMC free article] [PubMed] [Google Scholar]
  • 14.Waal Malefyt R., Abrams J., Bennet B., Figdor G., Vries J.E. IL-10 inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J. Exp. Med. 1991;174:1209–1209. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Lonnemann G., Endres C.A., Meer J.W.M., Cannon J.G., Koch K.M., Dinarello C.A. Differences in the synthesis and kinetics of release of Interleukin 1a, Interleukin 1b and tumor necrosis factor from human mononuclear cells. Eur. J. Immunol. 1989;19:1531–1531. doi: 10.1002/eji.1830190903. [DOI] [PubMed] [Google Scholar]
  • 16.Airoldi I., Saverino D., Favre A. Cytokine gene expression and T-cell proliferative responses in lymph node mononuclear cells from children with early stage human immunodeficiency virus infection. Hematologica. 2000;85:1237–1237. [PubMed] [Google Scholar]
  • 17.Khilnani P., Rajdev S.K., Uttam R. Pediatric AIDS: Part-1. Ind. J. Crit. Care Med. 2003;7(4):257–257. [Google Scholar]
  • 18.Madhivanan P., Mothi S.N., Kumarasamy N. Clinical manifestations of HIV infected children. Ind. J. Pediatr. 2003;70:615–615. doi: 10.1007/BF02724249. [DOI] [PubMed] [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. [PubMed]
  • 21.Chehimi J., Xiaojing M., Chouaib S. Differential production of interleukin 10 during human immunodeficiency virus infection. AIDS Res. Hum. Retro. 1996;12(12):1141–1141. doi: 10.1089/aid.1996.12.1141. [DOI] [PubMed] [Google Scholar]
  • 22.Clerici M., Balotta C., Meroni L., Ferrario E. Type 1 cytokine production and low prevalence of viral isolation correlate with long-term non-progression in HIV infection. AIDS Res. Hum. Retro. 1996;12(11):1053–1053. doi: 10.1089/aid.1996.12.1053. [DOI] [PubMed] [Google Scholar]
  • 23.Alimonti J.B., Ball T.B., Fowke K.R. Mechanisms of CD4+ T lymphocyte cell death in Human Immunodeficiency Virus infection and AIDS. J. Gen. Virol. 2003;84(7):1649–1649. doi: 10.1099/vir.0.19110-0. [DOI] [PubMed] [Google Scholar]
  • 24.Than S., Hu R., Oyaizu N. Cytokine pattern in relation to disease progression in human immunodeficiency virus-infected children. J. Infect. Dis. 1997;175(1):47–47. doi: 10.1093/infdis/175.1.47. [DOI] [PubMed] [Google Scholar]
  • 25.De S.K., Devadas K., Notkins A.L. 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. 2002;76(22):11710–11710. doi: 10.1128/JVI.76.22.11710-11714.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Bajaj J.S., Singh A., Aggarwal S.K., Chattopadhya D., Baveja U.K. Synergistic immunosuppression by candida in HIV infection: a cytokine based analysis. J. Commun. Dis. 2002;32(1):1–1. [PubMed] [Google Scholar]
  • 27.Crevel R., Karyadi E., Preyers F., Leenders M. 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. 2000;187(3):1194–1194. doi: 10.1086/315325. [DOI] [PubMed] [Google Scholar]
  • 28.Maggi E., Mazzetti M., Romagnani S. Ability of HIV to promote a Th1 to Th2 shift and to replicate preferentially in Th2 and Th0 cells. Science. 1994;265:244–244. doi: 10.1126/science.8023142. [DOI] [PubMed] [Google Scholar]
  • 29.Kazazi F., Mathijs J., Chang J. Recombinant interleukin 4 stimulates human immunodeficiency virus production by infected monocytes and macrophages. J. Gen. Virol. 1992;73:941–941. doi: 10.1099/0022-1317-73-4-941. [DOI] [PubMed] [Google Scholar]
  • 30.Meyaard L., Otto S.A., Keet I.P., Lier R.A., Miedema F. Changes in cytokine secretion pattern of CD4+ T clones in Human Immunodeficiency Virus infection. Blood. 1994;84(12):4262–4262. [PubMed] [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. [DOI] [PMC free article] [PubMed]
  • 32.Uittenbogaart C.H., Anisman D.J., Jack J.A. Effects of cytokines on HIV-1 production by thymocytes. Thymus. 1994;23(34):155–155. [PubMed] [Google Scholar]
  • 33.Bailer R., Holloway A., Sun J. 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. 1999;162(12):7534–7534. [PubMed] [Google Scholar]
  • 34.Atfeld M., Addo M., Kreuzer K. 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. 2000;23(4):287–287. doi: 10.1097/00126334-200004010-00001. [DOI] [PubMed] [Google Scholar]
  • 35.Tanaka M., Hirabayashi Y., Gatanaga H. 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(5):550–550. doi: 10.1046/j.1365-3083.1999.00627.x. [DOI] [PubMed] [Google Scholar]
  • 36.Meuller Brigitta, Pizzo Philip. Pediatric Human Immunodeficiency Virus Infections. In: DeVita V., editor. AIDS: Etiology, Diagnosis, Treatment and Prevention. 4th edition. Rosenberg: Hellman S.; 1997. pp. 443–464. [Google Scholar]
  • 37.Gordon S. Alternative activation of macrophages. Nat. Rev. Immunol. 2003;3(1):23–35. doi: 10.1038/nri978. [DOI] [PubMed] [Google Scholar]

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