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. 1990 Jun;64(6):2901–2906. doi: 10.1128/jvi.64.6.2901-2906.1990

Human immunodeficiency virus does not induce interleukin-1, interleukin-6, or tumor necrosis factor in mononuclear cells.

J M Molina 1, D T Scadden 1, C Amirault 1, A Woon 1, E Vannier 1, C A Dinarello 1, J E Groopman 1
PMCID: PMC249473  PMID: 2335821

Abstract

The production of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) by fresh peripheral blood mononuclear cells was evaluated after exposure to human immunodeficiency virus (HIV) or purified recombinant HIV-1 envelope glycoprotein (rgp120). To exclude the role of contaminating endotoxin in this study, all media were subjected to ultrafiltration and reagents contained less than 25 pg of endotoxin per ml by Limulus assay. Under endotoxin-free conditions, no increases in IL-1 beta, IL-6, or TNF-alpha mRNA or protein were detectable in cell cultures exposed to HIV-1, HIV-2, or rgp120 (0.1 to 10 micrograms/ml), as compared with cytokine levels in mock-exposed cultures. However, concentrations of endotoxin (lipopolysaccharide) as low as 0.5 ng/ml induced significant production of mRNA and protein for these three cytokines. Preincubation of mononuclear cells with "shake" HIV-1 preparations and also mock-infected shake preparations prior to lipopolysaccharide stimulation resulted in a two- to threefold increase in IL-1 beta and TNF-alpha production. This priming effect was not observed with rgp120 (0.1 to 10 micrograms/ml) or standard HIV-1 or mock-infected supernatants, suggesting the presence of biologically active material independent of virus in the shake preparations. Our studies indicate that, in the absence of endotoxin, HIV-1, HIV-2, and HIV gp120 do not induce production of IL-1 beta, IL-6, or TNF-alpha by peripheral blood mononuclear cells.

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Selected References

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

  1. Aderka D., Holtmann H., Toker L., Hahn T., Wallach D. Tumor necrosis factor induction by Sendai virus. J Immunol. 1986 Apr 15;136(8):2938–2942. [PubMed] [Google Scholar]
  2. Amento E. P., Kurnick J. T., Krane S. M. Interleukin 1 production by the human monocyte cell line U937 requires a lymphokine induction signal distinct from interleukin 2 or interferons. J Immunol. 1985 Jan;134(1):350–357. [PubMed] [Google Scholar]
  3. Arend W. P., Massoni R. J., Niemann M. A., Giclas P. C. Absence of induction of IL-1 production in human monocytes by complement fragments. J Immunol. 1989 Jan 1;142(1):173–178. [PubMed] [Google Scholar]
  4. Auron P. E., Webb A. C., Rosenwasser L. J., Mucci S. F., Rich A., Wolff S. M., Dinarello C. A. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907–7911. doi: 10.1073/pnas.81.24.7907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berman M. A., Sandborg C. I., Calabia B. S., Andrews B. S., Friou G. J. Interleukin 1 inhibitor masks high interleukin 1 production in acquired immunodeficiency syndrome (AIDS). Clin Immunol Immunopathol. 1987 Jan;42(1):133–140. doi: 10.1016/0090-1229(87)90180-2. [DOI] [PubMed] [Google Scholar]
  6. Beutler B., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
  7. Cavaillon J. M., Haeffner-Cavaillon N. Polymyxin-B inhibition of LPS-induced interleukin-1 secretion by human monocytes is dependent upon the LPS origin. Mol Immunol. 1986 Sep;23(9):965–969. doi: 10.1016/0161-5890(86)90127-6. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Clavel F., Guétard D., Brun-Vézinet F., Chamaret S., Rey M. A., Santos-Ferreira M. O., Laurent A. G., Dauguet C., Katlama C., Rouzioux C. Isolation of a new human retrovirus from West African patients with AIDS. Science. 1986 Jul 18;233(4761):343–346. doi: 10.1126/science.2425430. [DOI] [PubMed] [Google Scholar]
  10. Clouse K. A., Robbins P. B., Fernie B., Ostrove J. M., Fauci A. S. Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. J Immunol. 1989 Jul 15;143(2):470–475. [PubMed] [Google Scholar]
  11. Collman R., Hassan N. F., Walker R., Godfrey B., Cutilli J., Hastings J. C., Friedman H., Douglas S. D., Nathanson N. Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types. J Exp Med. 1989 Oct 1;170(4):1149–1163. doi: 10.1084/jem.170.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  13. Dinarello C. A. Interleukin-1 and its biologically related cytokines. Adv Immunol. 1989;44:153–205. doi: 10.1016/s0065-2776(08)60642-2. [DOI] [PubMed] [Google Scholar]
  14. Endres S., Ghorbani R., Lonnemann G., van der Meer J. W., Dinarello C. A. Measurement of immunoreactive interleukin-1 beta from human mononuclear cells: optimization of recovery, intrasubject consistency, and comparison with interleukin-1 alpha and tumor necrosis factor. Clin Immunol Immunopathol. 1988 Dec;49(3):424–438. doi: 10.1016/0090-1229(88)90130-4. [DOI] [PubMed] [Google Scholar]
  15. Fenton M. J., Clark B. D., Collins K. L., Webb A. C., Rich A., Auron P. E. Transcriptional regulation of the human prointerleukin 1 beta gene. J Immunol. 1987 Jun 1;138(11):3972–3979. [PubMed] [Google Scholar]
  16. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  17. Gendelman H. E., Orenstein J. M., Martin M. A., Ferrua C., Mitra R., Phipps T., Wahl L. A., Lane H. C., Fauci A. S., Burke D. S. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med. 1988 Apr 1;167(4):1428–1441. doi: 10.1084/jem.167.4.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Groopman J. E., Benz P. M., Ferriani R., Mayer K., Allan J. D., Weymouth L. A. Characterization of serum neutralization response to the human immunodeficiency virus (HIV). AIDS Res Hum Retroviruses. 1987 Spring;3(1):71–85. doi: 10.1089/aid.1987.3.71. [DOI] [PubMed] [Google Scholar]
  19. Johnston R. B., Jr Current concepts: immunology. Monocytes and macrophages. N Engl J Med. 1988 Mar 24;318(12):747–752. doi: 10.1056/NEJM198803243181205. [DOI] [PubMed] [Google Scholar]
  20. Kishimoto T. The biology of interleukin-6. Blood. 1989 Jul;74(1):1–10. [PubMed] [Google Scholar]
  21. Lasky L. A., Groopman J. E., Fennie C. W., Benz P. M., Capon D. J., Dowbenko D. J., Nakamura G. R., Nunes W. M., Renz M. E., Berman P. W. Neutralization of the AIDS retrovirus by antibodies to a recombinant envelope glycoprotein. Science. 1986 Jul 11;233(4760):209–212. doi: 10.1126/science.3014647. [DOI] [PubMed] [Google Scholar]
  22. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  23. Lepe-Zuniga J. L., Mansell P. W., Hersh E. M. Idiopathic production of interleukin-1 in acquired immune deficiency syndrome. J Clin Microbiol. 1987 Sep;25(9):1695–1700. doi: 10.1128/jcm.25.9.1695-1700.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lähdevirta J., Maury C. P., Teppo A. M., Repo H. Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome. Am J Med. 1988 Sep;85(3):289–291. doi: 10.1016/0002-9343(88)90576-1. [DOI] [PubMed] [Google Scholar]
  25. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Mizel S. B., Oppenheim J. J., Rosenstreich D. L. Characterization of lymphocyte-activating factor (LAF) produced by the macrophage cell line, P388D1. I. Enhancement of LAF production by activated T lymphocytes. J Immunol. 1978 May;120(5):1497–1503. [PubMed] [Google Scholar]
  28. Molina J. M., Scadden D. T., Byrn R., Dinarello C. A., Groopman J. E. Production of tumor necrosis factor alpha and interleukin 1 beta by monocytic cells infected with human immunodeficiency virus. J Clin Invest. 1989 Sep;84(3):733–737. doi: 10.1172/JCI114230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Moore R. N., Oppenheim J. J., Farrar J. J., Carter C. S., Jr, Waheed A., Shadduck R. K. Production of lymphocyte-activating factor (Interleukin 1) by macrophages activated with colony-stimulating factors. J Immunol. 1980 Sep;125(3):1302–1305. [PubMed] [Google Scholar]
  30. Nakajima K., Martínez-Maza O., Hirano T., Breen E. C., Nishanian P. G., Salazar-Gonzalez J. F., Fahey J. L., Kishimoto T. Induction of IL-6 (B cell stimulatory factor-2/IFN-beta 2) production by HIV. J Immunol. 1989 Jan 15;142(2):531–536. [PubMed] [Google Scholar]
  31. Newton R. C. Human monocyte production of interleukin-1: parameters of the induction of interleukin-1 secretion by lipopolysaccharides. J Leukoc Biol. 1986 Mar;39(3):299–311. doi: 10.1002/jlb.39.3.299. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Pennica D., Nedwin G. E., Hayflick J. S., Seeburg P. H., Derynck R., Palladino M. A., Kohr W. J., Aggarwal B. B., Goeddel D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. doi: 10.1038/312724a0. [DOI] [PubMed] [Google Scholar]
  34. Robbins D. S., Shirazi Y., Drysdale B. E., Lieberman A., Shin H. S., Shin M. L. Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes. J Immunol. 1987 Oct 15;139(8):2593–2597. [PubMed] [Google Scholar]
  35. Roberts N. J., Jr, Prill A. H., Mann T. N. Interleukin 1 and interleukin 1 inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus. Respiratory syncytial virus is a potent inducer of inhibitor activity. J Exp Med. 1986 Mar 1;163(3):511–519. doi: 10.1084/jem.163.3.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Salzman G. C., Crowell J. M., Martin J. C., Trujillo T. T., Romero A., Mullaney P. F., LaBauve P. M. Cell classification by laser light scattering: identification and separation of unstained leukocytes. Acta Cytol. 1975 Jul-Aug;19(4):374–377. [PubMed] [Google Scholar]
  38. Schindler R., Dinarello C. A. A method for removing interleukin-1- and tumor necrosis factor-inducing substances from bacterial cultures by ultrafiltration with polysulfone. J Immunol Methods. 1989 Jan 17;116(2):159–165. doi: 10.1016/0022-1759(89)90199-3. [DOI] [PubMed] [Google Scholar]
  39. Schindler R., Mancilla J., Endres S., Ghorbani R., Clark S. C., Dinarello C. A. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990 Jan 1;75(1):40–47. [PubMed] [Google Scholar]
  40. Siliciano R. F., Knall C., Lawton T., Berman P., Gregory T., Reinherz E. L. Recognition of HIV glycoprotein gp120 by T cells. Role of monocyte CD4 in the presentation of gp120. J Immunol. 1989 Mar 1;142(5):1506–1511. [PubMed] [Google Scholar]
  41. Tschachler E., Robert-Guroff M., Gallo R. C., Reitz M. S., Jr Human T-lymphotropic virus I-infected T cells constitutively express lymphotoxin in vitro. Blood. 1989 Jan;73(1):194–201. [PubMed] [Google Scholar]
  42. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Vujcic L. K., Shepp D. H., Klutch M., Wells M. A., Hendry R. M., Wittek A. E., Krilov L., Quinnan G. V., Jr Use of a sensitive neutralization assay to measure the prevalence of antibodies to the human immunodeficiency virus. J Infect Dis. 1988 May;157(5):1047–1050. doi: 10.1093/infdis/157.5.1047. [DOI] [PubMed] [Google Scholar]
  44. Wahl L. M., Corcoran M. L., Pyle S. W., Arthur L. O., Harel-Bellan A., Farrar W. L. Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. Proc Natl Acad Sci U S A. 1989 Jan;86(2):621–625. doi: 10.1073/pnas.86.2.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wong G. G., Witek-Giannotti J. S., Temple P. A., Kriz R., Ferenz C., Hewick R. M., Clark S. C., Ikebuchi K., Ogawa M. Stimulation of murine hemopoietic colony formation by human IL-6. J Immunol. 1988 May 1;140(9):3040–3044. [PubMed] [Google Scholar]
  46. Wright S. C., Jewett A., Mitsuyasu R., Bonavida B. Spontaneous cytotoxicity and tumor necrosis factor production by peripheral blood monocytes from AIDS patients. J Immunol. 1988 Jul 1;141(1):99–104. [PubMed] [Google Scholar]
  47. van der Meer J. W., Endres S., Lonnemann G., Cannon J. G., Ikejima T., Okusawa S., Gelfand J. A., Dinarello C. A. Concentrations of immunoreactive human tumor necrosis factor alpha produced by human mononuclear cells in vitro. J Leukoc Biol. 1988 Mar;43(3):216–223. doi: 10.1002/jlb.43.3.216. [DOI] [PubMed] [Google Scholar]

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