Abstract
We measured plasma concentrations of soluble receptors for IL-2 (sIL-2R) and tumour necrosis factor-alpha (TNF-alpha) in 149 haemophilia patients. Soluble IL-2R levels were elevated in 37% of 62 HIV-seronegative patients (mean 570 +/- 27 U/ml versus 361 +/- 17 U/ml in the control group, P less than 0.0001), in 78% of 68 HIV-seropositive patients (928 +/- 49 U/ml, P less than 0.0001), and in 95% of 19 AIDS/ARC patients (1578 +/- 199 U/ml, P less than 0.0001 compared with controls and with HIV-seronegative patients; P less than 0.005 compared with HIV-seropositive asymptomatic patients). A negative correlation was observed between sIL-2R, relative and absolute numbers of CD4+ cells (P less than 0.0001), and CD4/CD8 ratios (P less than 0.0001). There was also a negative correlation between sIL-2R in plasma and the cellular expression of IL-2R (P less than 0.001). We found a significant association of sIL-2R and plasma neopterin (P less than 0.0001). With progression of the disease from HIV-seronegative to seropositive without symptoms and to full manifestation of AIDS/ARC, sIL-2R plasma levels increased. The highest levels were found at the time of diagnosis of AIDS/ARC, but the levels decreased again during the following 18 months. Eight per cent of HIV-seronegative patients, 32% of HIV-seropositive patients, and 24% of patients with AIDS/ARC had increased plasma TNF-alpha. We conclude that sIL-2R and TNF-alpha plasma levels are elevated in HIV-infected haemophilia patients and that sIL-2R is a marker for disease progression from asymptomatic HIV-seropositive to AIDS/ARC.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Beutler B., Greenwald D., Hulmes J. D., Chang M., Pan Y. C., Mathison J., Ulevitch R., Cerami A. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature. 1985 Aug 8;316(6028):552–554. doi: 10.1038/316552a0. [DOI] [PubMed] [Google Scholar]
- Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
- Beutler B., Mahoney J., Le Trang N., Pekala P., Cerami A. Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J Exp Med. 1985 May 1;161(5):984–995. doi: 10.1084/jem.161.5.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Daniel V., Opelz G., Schäfer A., Schimpf K., Wendler I., Hunsmann G. Correlation of immune defects in hemophilia with HTLV-III antibody titers. Vox Sang. 1986;51(1):35–39. doi: 10.1111/j.1423-0410.1986.tb00205.x. [DOI] [PubMed] [Google Scholar]
- Fahey J. L., Taylor J. M., Detels R., Hofmann B., Melmed R., Nishanian P., Giorgi J. V. The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1. N Engl J Med. 1990 Jan 18;322(3):166–172. doi: 10.1056/NEJM199001183220305. [DOI] [PubMed] [Google Scholar]
- Flick D. A., Gifford G. E. Pharmacokinetics of murine tumor necrosis factor. J Immunopharmacol. 1986;8(1):89–97. doi: 10.3109/08923978609031087. [DOI] [PubMed] [Google Scholar]
- Folks T. M., Justement J., Kinter A., Schnittman S., Orenstein J., Poli G., Fauci A. S. Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate. J Immunol. 1988 Feb 15;140(4):1117–1122. [PubMed] [Google Scholar]
- Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
- Gupta S. Study of activated T cells in man. II. Interleukin 2 receptor and transferrin receptor expression on T cells and production of interleukin 2 in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex. Clin Immunol Immunopathol. 1986 Jan;38(1):93–100. doi: 10.1016/0090-1229(86)90126-1. [DOI] [PubMed] [Google Scholar]
- Hackett R. J., Davis L. S., Lipsky P. E. Comparative effects of tumor necrosis factor-alpha and IL-1 beta on mitogen-induced T cell activation. J Immunol. 1988 Apr 15;140(8):2639–2644. [PubMed] [Google Scholar]
- Hober D., Haque A., Wattre P., Beaucaire G., Mouton Y., Capron A. Production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) in patients with AIDS. Enhanced level of TNF-alpha is related to a higher cytotoxic activity. Clin Exp Immunol. 1989 Dec;78(3):329–333. [PMC free article] [PubMed] [Google Scholar]
- Honda M., Kitamura K., Matsuda K., Yokota Y., Yamamoto N., Mitsuyasu R., Chermann J. C., Tokunaga T. Soluble IL-2 receptor in AIDS. Correlation of its serum level with the classification of HIV-induced diseases and its characterization. J Immunol. 1989 Jun 15;142(12):4248–4255. [PubMed] [Google Scholar]
- Kloster B. E., John P. A., Miller L. E., Rubin L. A., Nelson D. L., Blair D. C., Tomar R. H. Soluble interleukin 2 receptors are elevated in patients with AIDS or at risk of developing AIDS. Clin Immunol Immunopathol. 1987 Dec;45(3):440–446. doi: 10.1016/0090-1229(87)90095-x. [DOI] [PubMed] [Google Scholar]
- Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., Janotta F., Aksamit A., Martin M. A., Fauci A. S. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986 Sep 5;233(4768):1089–1093. doi: 10.1126/science.3016903. [DOI] [PubMed] [Google Scholar]
- Koyanagi Y., Harada S., Takahashi M., Uchino F., Yamamoto N. Selective cytotoxicity of AIDS virus infection towards HTLV-I-transformed cell lines. Int J Cancer. 1985 Oct 15;36(4):445–451. doi: 10.1002/ijc.2910360406. [DOI] [PubMed] [Google Scholar]
- Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
- 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]
- Margolick J. B., Volkman D. J., Folks T. M., Fauci A. S. Amplification of HTLV-III/LAV infection by antigen-induced activation of T cells and direct suppression by virus of lymphocyte blastogenic responses. J Immunol. 1987 Mar 15;138(6):1719–1723. [PubMed] [Google Scholar]
- Martínez-Maza O., Crabb E., Mitsuyasu R. T., Fahey J. L., Giorgi J. V. Infection with the human immunodeficiency virus (HIV) is associated with an in vivo increase in B lymphocyte activation and immaturity. J Immunol. 1987 Jun 1;138(11):3720–3724. [PubMed] [Google Scholar]
- Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Pitha P. M. Herpes simplex virus type-1 can reactivate transcription of latent human immunodeficiency virus. Nature. 1987 Jan 1;325(6099):67–70. doi: 10.1038/325067a0. [DOI] [PubMed] [Google Scholar]
- Nilsson I. M., Berntorp E., Zettervall O. Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII. N Engl J Med. 1988 Apr 14;318(15):947–950. doi: 10.1056/NEJM198804143181503. [DOI] [PubMed] [Google Scholar]
- Okamoto T., Matsuyama T., Mori S., Hamamoto Y., Kobayashi N., Yamamoto N., Josephs S. F., Wong-Staal F., Shimotohno K. Augmentation of human immunodeficiency virus type 1 gene expression by tumor necrosis factor alpha. AIDS Res Hum Retroviruses. 1989 Apr;5(2):131–138. doi: 10.1089/aid.1989.5.131. [DOI] [PubMed] [Google Scholar]
- Prince H. E., Kleinman S., Williams A. E. Soluble IL-2 receptor levels in serum from blood donors seropositive for HIV. J Immunol. 1988 Feb 15;140(4):1139–1141. [PubMed] [Google Scholar]
- Quinn T. C., Piot P., McCormick J. B., Feinsod F. M., Taelman H., Kapita B., Stevens W., Fauci A. S. Serologic and immunologic studies in patients with AIDS in North America and Africa. The potential role of infectious agents as cofactors in human immunodeficiency virus infection. JAMA. 1987 May 15;257(19):2617–2621. [PubMed] [Google Scholar]
- Reddy M. M., Grieco M. H. Elevated soluble interleukin-2 receptor levels in serum of human immunodeficiency virus infected populations. AIDS Res Hum Retroviruses. 1988 Apr;4(2):115–120. doi: 10.1089/aid.1988.4.115. [DOI] [PubMed] [Google Scholar]
- Rosenberg Z. F., Fauci A. S. Immunopathogenic mechanisms of HIV infection. Clin Immunol Immunopathol. 1989 Jan;50(1 Pt 2):S149–S156. doi: 10.1016/0090-1229(89)90122-0. [DOI] [PubMed] [Google Scholar]
- Rubin L. A., Kurman C. C., Fritz M. E., Biddison W. E., Boutin B., Yarchoan R., Nelson D. L. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol. 1985 Nov;135(5):3172–3177. [PubMed] [Google Scholar]
- Rudy T., Opelz G., Gerlach R., Daniel V., Schimpf K. Correlation of in vitro immune defects with impaired gamma interferon response in human-immunodeficiency-virus-infected individuals. Vox Sang. 1988;54(2):92–95. doi: 10.1111/j.1423-0410.1988.tb01623.x. [DOI] [PubMed] [Google Scholar]
- Salahuddin S. Z., Rose R. M., Groopman J. E., Markham P. D., Gallo R. C. Human T lymphotropic virus type III infection of human alveolar macrophages. Blood. 1986 Jul;68(1):281–284. [PubMed] [Google Scholar]
- Sugamura K., Fujii M., Kobayashi N., Sakitani M., Hatanaka M., Hinuma Y. Retrovirus-induced expression of interleukin 2 receptors on cells of human B-cell lineage. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7441–7445. doi: 10.1073/pnas.81.23.7441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valitutti S., Carbone A., Castellino F., Maggiano N., Ricci R., Larocca L. M., Musiani P. The expression of functional IL-2 receptor on activated macrophages depends on the stimulus applied. Immunology. 1989 May;67(1):44–50. [PMC free article] [PubMed] [Google Scholar]
- Voth R., Rossol S., Klein K., Hess G., Schütt K. H., Schröder H. C., Meyer zum Büschenfelde K. H., Müller W. E. Differential gene expression of IFN-alpha and tumor necrosis factor-alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS. J Immunol. 1990 Feb 1;144(3):970–975. [PubMed] [Google Scholar]
- Waage A. Production and clearance of tumor necrosis factor in rats exposed to endotoxin and dexamethasone. Clin Immunol Immunopathol. 1987 Dec;45(3):348–355. doi: 10.1016/0090-1229(87)90087-0. [DOI] [PubMed] [Google Scholar]
- Weimer R., Daniel V., Zimmermann R., Schimpf K., Opelz G. Autoantibodies against CD4 cells are associated with CD4 helper defects in human immunodeficiency virus-infected patients. Blood. 1991 Jan 1;77(1):133–140. [PubMed] [Google Scholar]
- 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]