Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jan 4;91(1):108–112. doi: 10.1073/pnas.91.1.108

Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist.

G Poli 1, A L Kinter 1, A S Fauci 1
PMCID: PMC42895  PMID: 7506410

Abstract

In the present study we have observed that interleukin (IL) 1 alpha or IL-1 beta directly induced expression of human immunodeficiency virus (HIV) in the latently infected human promonocytic cell line U1. In addition, IL-1 synergized with IL-6, but not with tumor necrosis factor, in the upregulation of virus expression in U1 cells as measured by accumulation of steady-state mRNAs and production of reverse transcriptase activity. The HIV inductive effect of IL-1 was blocked by transforming growth factor beta, anti-IL-1 antibodies, or monoclonal antibodies directed to the type 1, but not to the type 2, cell surface receptor for IL-1; the latter actually caused enhancement of the IL-1-mediated effect. Unlike tumor necrosis factor alpha, IL-1 either alone or in combination with IL-6 did not induce activation of the transcription activating factor NF-kappa B above the constitutive levels of unstimulated U1 cells. Finally, the IL-1 receptor antagonist effectively blocked IL-1-mediated direct and synergistic inductive effects on virus production. Thus, IL-1 may be an important mediator of HIV expression, and blocking of IL-1 expression and/or its effects may have a potential therapeutic role in the inhibition of HIV expression in infected individuals.

Full text

PDF
111

Images in this article

109Fig. 2
on p.109
110Fig. 3
on p.110

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baldari C. T., Macchia G., Massone A., Telford J. L. p21ras contributes to HIV-1 activation in T-cells. FEBS Lett. 1992 Jun 15;304(2-3):261–264. doi: 10.1016/0014-5793(92)80633-r. [DOI] [PubMed] [Google Scholar]
  2. Bressler P., Pantaleo G., Demaria A., Fauci A. S. Anti-CD2 receptor antibodies activate the HIV long terminal repeat in T lymphocytes. J Immunol. 1991 Oct 1;147(7):2290–2294. [PubMed] [Google Scholar]
  3. Clouse K. A., Powell D., Washington I., Poli G., Strebel K., Farrar W., Barstad P., Kovacs J., Fauci A. S., Folks T. M. Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J Immunol. 1989 Jan 15;142(2):431–438. [PubMed] [Google Scholar]
  4. Colotta F., Re F., Muzio M., Bertini R., Polentarutti N., Sironi M., Giri J. G., Dower S. K., Sims J. E., Mantovani A. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science. 1993 Jul 23;261(5120):472–475. doi: 10.1126/science.8332913. [DOI] [PubMed] [Google Scholar]
  5. D'Addario M., Wainberg M. A., Hiscott J. Activation of cytokine genes in HIV-1 infected myelomonoblastic cells by phorbol ester and tumor necrosis factor. J Immunol. 1992 Feb 15;148(4):1222–1229. [PubMed] [Google Scholar]
  6. Dinarello C. A., Thompson R. C. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today. 1991 Nov;12(11):404–410. doi: 10.1016/0167-5699(91)90142-G. [DOI] [PubMed] [Google Scholar]
  7. Dreno B., Milpied B., Dutartre H., Litoux P. Epidermal interleukin 1 in normal skin of patients with HIV infection. Br J Dermatol. 1990 Oct;123(4):487–492. doi: 10.1111/j.1365-2133.1990.tb01454.x. [DOI] [PubMed] [Google Scholar]
  8. Duh E. J., Maury W. J., Folks T. M., Fauci A. S., Rabson A. B. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974–5978. doi: 10.1073/pnas.86.15.5974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Embretson J., Zupancic M., Ribas J. L., Burke A., Racz P., Tenner-Racz K., Haase A. T. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. doi: 10.1038/362359a0. [DOI] [PubMed] [Google Scholar]
  10. Emilie D., Peuchmaur M., Maillot M. C., Crevon M. C., Brousse N., Delfraissy J. F., Dormont J., Galanaud P. Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes. J Clin Invest. 1990 Jul;86(1):148–159. doi: 10.1172/JCI114678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
  12. Folks T. M., Justement J., Kinter A., Dinarello C. A., Fauci A. S. Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science. 1987 Nov 6;238(4828):800–802. doi: 10.1126/science.3313729. [DOI] [PubMed] [Google Scholar]
  13. Gallo P., Frei K., Rordorf C., Lazdins J., Tavolato B., Fontana A. Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid. J Neuroimmunol. 1989 Jul;23(2):109–116. doi: 10.1016/0165-5728(89)90029-5. [DOI] [PubMed] [Google Scholar]
  14. Grilli M., Chiu J. J., Lenardo M. J. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993;143:1–62. doi: 10.1016/s0074-7696(08)61873-2. [DOI] [PubMed] [Google Scholar]
  15. Kobayashi N., Hamamoto Y., Koyanagi Y., Chen I. S., Yamamoto N. Effect of interleukin-1 on the augmentation of human immunodeficiency virus gene expression. Biochem Biophys Res Commun. 1989 Dec 15;165(2):715–721. doi: 10.1016/s0006-291x(89)80025-7. [DOI] [PubMed] [Google Scholar]
  16. Krasnow S. W., Zhang L. Q., Leung K. Y., Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor-alpha, interleukin 1, and phorbol myristate acetate are independent activators of NF-kappa B which differentially activate T cells. Cytokine. 1991 Sep;3(5):372–379. doi: 10.1016/1043-4666(91)90040-k. [DOI] [PubMed] [Google Scholar]
  17. Meltzer M. S., Skillman D. R., Hoover D. L., Hanson B. D., Turpin J. A., Kalter D. C., Gendelman H. E. Macrophages and the human immunodeficiency virus. Immunol Today. 1990 Jun;11(6):217–223. doi: 10.1016/0167-5699(90)90086-o. [DOI] [PubMed] [Google Scholar]
  18. Merrill J. E., Koyanagi Y., Chen I. S. Interleukin-1 and tumor necrosis factor alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor. J Virol. 1989 Oct;63(10):4404–4408. doi: 10.1128/jvi.63.10.4404-4408.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ohlsson K., Björk P., Bergenfeldt M., Hageman R., Thompson R. C. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990 Dec 6;348(6301):550–552. doi: 10.1038/348550a0. [DOI] [PubMed] [Google Scholar]
  20. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. doi: 10.1038/362355a0. [DOI] [PubMed] [Google Scholar]
  22. Poli G., Bottazzi B., Acero R., Bersani L., Rossi V., Introna M., Lazzarin A., Galli M., Mantovani A. Monocyte function in intravenous drug abusers with lymphadenopathy syndrome and in patients with acquired immunodeficiency syndrome: selective impairment of chemotaxis. Clin Exp Immunol. 1985 Oct;62(1):136–142. [PMC free article] [PubMed] [Google Scholar]
  23. Poli G., Bressler P., Kinter A., Duh E., Timmer W. C., Rabson A., Justement J. S., Stanley S., Fauci A. S. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J Exp Med. 1990 Jul 1;172(1):151–158. doi: 10.1084/jem.172.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Poli G., Fauci A. S. The role of monocyte/macrophages and cytokines in the pathogenesis of HIV infection. Pathobiology. 1992;60(4):246–251. doi: 10.1159/000163729. [DOI] [PubMed] [Google Scholar]
  25. Poli G., Kinter A. L., Justement J. S., Bressler P., Kehrl J. H., Fauci A. S. Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage. J Exp Med. 1991 Mar 1;173(3):589–597. doi: 10.1084/jem.173.3.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Poli G., Kinter A., Justement J. S., Kehrl J. H., Bressler P., Stanley S., Fauci A. S. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci U S A. 1990 Jan;87(2):782–785. doi: 10.1073/pnas.87.2.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Roux-Lombard P., Modoux C., Cruchaud A., Dayer J. M. Purified blood monocytes from HIV 1-infected patients produce high levels of TNF alpha and IL-1. Clin Immunol Immunopathol. 1989 Mar;50(3):374–384. doi: 10.1016/0090-1229(89)90144-x. [DOI] [PubMed] [Google Scholar]
  28. Schuitemaker H., Kootstra N. A., Koppelman M. H., Bruisten S. M., Huisman H. G., Tersmette M., Miedema F. Proliferation-dependent HIV-1 infection of monocytes occurs during differentiation into macrophages. J Clin Invest. 1992 Apr;89(4):1154–1160. doi: 10.1172/JCI115697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sims J. E., Gayle M. A., Slack J. L., Alderson M. R., Bird T. A., Giri J. G., Colotta F., Re F., Mantovani A., Shanebeck K. Interleukin 1 signaling occurs exclusively via the type I receptor. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6155–6159. doi: 10.1073/pnas.90.13.6155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Slack J., McMahan C. J., Waugh S., Schooley K., Spriggs M. K., Sims J. E., Dower S. K. Independent binding of interleukin-1 alpha and interleukin-1 beta to type I and type II interleukin-1 receptors. J Biol Chem. 1993 Feb 5;268(4):2513–2524. [PubMed] [Google Scholar]
  31. Steffen M., Reinecker H. C., Petersen J., Doehn C., Pflüger I., Voss A., Raedler A. Differences in cytokine secretion by intestinal mononuclear cells, peripheral blood monocytes and alveolar macrophages from HIV-infected patients. Clin Exp Immunol. 1993 Jan;91(1):30–36. doi: 10.1111/j.1365-2249.1993.tb03349.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Swingler S., Easton A., Morris A. Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells. AIDS Res Hum Retroviruses. 1992 Apr;8(4):487–493. doi: 10.1089/aid.1992.8.487. [DOI] [PubMed] [Google Scholar]
  33. Twigg H. L., 3rd, Iwamoto G. K., Soliman D. M. Role of cytokines in alveolar macrophage accessory cell function in HIV-infected individuals. J Immunol. 1992 Aug 15;149(4):1462–1469. [PubMed] [Google Scholar]
  34. Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. von Briesen H., von Mallinckrodt C., Esser R., Müller S., Becker K., Rübsamen-Waigmann H., Andreesen R. Effect of cytokines and lipopolysaccharides on HIV infection of human macrophages. Res Virol. 1991 Mar-Jun;142(2-3):197–204. doi: 10.1016/0923-2516(91)90057-a. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES