FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 332:567-575 March 2, 1995 Number 9 Next

	Full Text PDF Letters Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Interleukin-2 is an important regulatory cytokine of the immune system, with potent effects on T cells, B cells, and natural killer cells. In vitro, interleukin-2 can induce the proliferation and differentiation of peripheral-blood mononuclear cells from patients infected with the human immunodeficiency virus (HIV).

Methods We treated 25 HIV-infected patients with interleukin-2 administered as a continuous infusion at a dosage of 6 to 18 million IU per day for 5 days every 8 weeks during a period of 7 to 25 months. All patients also received at least one approved antiviral agent. Immunologic and virologic variables were monitored monthly.

Results In 6 of 10 patients with base-line CD4 counts higher than 200 per cubic millimeter, interleukin-2 therapy was associated with at least a 50 percent increase in the number of CD4 cells. Changes ranged from -81 to +2211 cells per cubic millimeter. Interleukin-2 therapy resulted in a decline in the percentage of CD8 lymphocytes expressing HLA-DR and an increase in the percentage of CD4 lymphocytes that were positive for the p55 chain of the interleukin-2 receptor. Four patients had a transient but consistent increase in the plasma HIV RNA level at the end of each infusion. In the remaining 15 patients, who had CD4 counts of 200 or fewer cells per cubic millimeter, interleukin-2 therapy was associated with increased viral activation, few immunologic improvements, and substantial toxic effects.

Conclusions Intermittent courses of interleukin-2 can improve some of the immunologic abnormalities associated with HIV infection in patients with more than 200 CD4 cells per cubic millimeter.

Source Information

From the Critical Care Medicine Department, Warren Grant Magnuson Clinical Center (J.A.K., H.M.), and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (S.V., R.T.D., J.F., M.A.P., R.E.W., J.A.M., H.C.L.), Bethesda, Md.; and Program Resources, Inc./DynCorp, Frederick, Md. (M.B., R.J.D., R.S., N.P.S.).

Address reprint requests to Dr. Lane at the National Institutes of Health, Bldg. 10, Rm 11B-13, Bethesda, MD 20892.

Full Text of this Article

Related Letters:

Interleukin-2 as Therapy for HIV Disease
Disla E., Goldberg B., Landonio G., Baiocchi C., Ferrari M., Lane H. C., Kovacs J. A.
Extract | Full Text  
N Engl J Med 1995; 333:192-193, Jul 20, 1995. Correspondence

Interleukin-2 Infusions in HIV-Infected Patients
Jacobson E. L., Pilaro F., Smith K. A., Kovacs J. A., Davey R. T., Lane H. C.
Extract | Full Text  
N Engl J Med 1997; 336:1260-1261, Apr 24, 1997. Correspondence

This article has been cited by other articles:

• Sportes, C., Hakim, F. T., Memon, S. A., Zhang, H., Chua, K. S., Brown, M. R., Fleisher, T. A., Krumlauf, M. C., Babb, R. R., Chow, C. K., Fry, T. J., Engels, J., Buffet, R., Morre, M., Amato, R. J., Venzon, D. J., Korngold, R., Pecora, A., Gress, R. E., Mackall, C. L. (2008). Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J. Exp. Med. 205: 1701-1714 [Abstract] [Full Text]  
• Crotti, A., Lusic, M., Lupo, R., Lievens, P. M. J., Liboi, E., Chiara, G. D., Tinelli, M., Lazzarin, A., Patterson, B. K., Giacca, M., Bovolenta, C., Poli, G. (2007). Naturally occurring C-terminally truncated STAT5 is a negative regulator of HIV-1 expression. Blood 109: 5380-5389 [Abstract] [Full Text]  
• Cesana, G. C., Romano, F., Piacentini, G., Scotti, M., Brenna, A., Bovo, G., Vaghi, M., Aletti, G., Caprotti, R., Kaufman, H., Uggeri, F. (2007). Low-dose Interleukin-2 Administered Pre-operatively to Patients with Gastric Cancer Activates Peripheral and Peritumoral Lymphocytes But Does Not Affect Prognosis. Ann. Surg. Oncol. 14: 1295-1304 [Abstract] [Full Text]  
• Mitsuyasu, R., Gelman, R., Cherng, D. W., Landay, A., Fahey, J., Reichman, R., Erice, A., Bucy, R. P., Kilby, J. M., Lederman, M. M., Hamilton, C. D., Lertora, J., White, B. L., Tebas, P., Duliege, A.-M., Pollard, R. B., for the AIDS Clinical Trials Group 328 Study Team, (2007). The Virologic, Immunologic, and Clinical Effects of Interleukin 2 With Potent Antiretroviral Therapy in Patients With Moderately Advanced Human Immunodeficiency Virus Infection: A Randomized Controlled Clinical Trial--AIDS Clinical Trials Group 328. Arch Intern Med 167: 597-605 [Abstract] [Full Text]  
• Shah, M. H., Freud, A. G., Benson, D. M. Jr., Ferkitich, A. K., Dezube, B. J., Bernstein, Z. P., Caligiuri, M. A. (2006). A Phase I Study of Ultra Low Dose Interleukin-2 and Stem Cell Factor in Patients with HIV Infection or HIV and Cancer.. Clin. Cancer Res. 12: 3993-3996 [Abstract] [Full Text]  
• Kasamon, Y. L., Flinn, I. W., Grever, M. R., Diehl, L. F., Garrett-Mayer, E., Goodman, S. N., Lucas, M. S., Byrd, J. C. (2005). Phase I Study of Low-Dose Interleukin-2, Fludarabine, and Cyclophosphamide for Previously Untreated Indolent Lymphoma and Chronic Lymphocytic Leukemia. Clin. Cancer Res. 11: 8413-8417 [Abstract] [Full Text]  
• Nacsa, J., Edghill-Smith, Y., Tsai, W.-P., Venzon, D., Tryniszewska, E., Hryniewicz, A., Moniuszko, M., Kinter, A., Smith, K. A., Franchini, G. (2005). Contrasting Effects of Low-Dose IL-2 on Vaccine-Boosted Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cells in Macaques Chronically Infected with SIVmac251. J. Immunol. 174: 1913-1921 [Abstract] [Full Text]  
• Farel, C. E., Chaitt, D. G., Hahn, B. K., Tavel, J. A., Kovacs, J. A., Polis, M. A., Masur, H., Follmann, D. A., Lane, H. C., Davey, R. T. Jr (2004). Induction and maintenance therapy with intermittent interleukin-2 in HIV-1 infection. Blood 103: 3282-3286 [Abstract] [Full Text]  
• Rubinstein, M. P., Kadima, A. N., Salem, M. L., Nguyen, C. L., Gillanders, W. E., Cole, D. J. (2002). Systemic Administration of IL-15 Augments the Antigen-Specific Primary CD8+ T Cell Response Following Vaccination with Peptide-Pulsed Dendritic Cells. J. Immunol. 169: 4928-4935 [Abstract] [Full Text]  
• Richardson, J., Broche, S., Baud, S., Leste-Lasserre, T., Femenia, F., Levy, D., Moraillon, A., Pancino, G., Sonigo, P. (2002). Lymphoid activation: a confounding factor in AIDS vaccine development?. J. Gen. Virol. 83: 2515-2521 [Abstract] [Full Text]  
• Sereti, I., Martinez-Wilson, H., Metcalf, J. A., Baseler, M. W., Hallahan, C. W., Hahn, B., Hengel, R. L., Davey, R. T., Kovacs, J. A., Lane, H. C. (2002). Long-term effects of intermittent interleukin 2 therapy in patients with HIV infection: characterization of a novel subset of CD4+/CD25+ T cells. Blood 100: 2159-2167 [Abstract] [Full Text]  
• Natarajan, V., Lempicki, R. A., Sereti, I., Badralmaa, Y., Adelsberger, J. W., Metcalf, J. A., Prieto, D. A., Stevens, R., Baseler, M. W., Kovacs, J. A., Lane, H. C. (2002). Increased peripheral expansion of naive CD4+ T cells in vivo after IL-2 treatment of patients with HIV infection. Proc. Natl. Acad. Sci. USA 99: 10712-10717 [Abstract] [Full Text]  
• Yeni, P. G., Hammer, S. M., Carpenter, C. C. J., Cooper, D. A., Fischl, M. A., Gatell, J. M., Gazzard, B. G., Hirsch, M. S., Jacobsen, D. M., Katzenstein, D. A., Montaner, J. S. G., Richman, D. D., Saag, M. S., Schechter, M., Schooley, R. T., Thompson, M. A., Vella, S., Volberding, P. A. (2002). Antiretroviral Treatment for Adult HIV Infection in 2002: Updated Recommendations of the International AIDS Society-USA Panel. JAMA 288: 222-235 [Abstract] [Full Text]  
• De Paoli, P. (2001). Immunological Effects of Interleukin-2 Therapy in Human Immunodeficiency Virus-Positive Subjects. CVI 8: 671-677 [Full Text]  
• Trimble, L. A., Shankar, P., Patterson, M., Daily, J. P., Lieberman, J. (2000). Human Immunodeficiency Virus-Specific Circulating CD8 T Lymphocytes Have Down-Modulated CD3zeta and CD28, Key Signaling Molecules for T-Cell Activation. J. Virol. 74: 7320-7330 [Abstract] [Full Text]  
• Davey, R. T. Jr, Murphy, R. L., Graziano, F. M., Boswell, S. L., Pavia, A. T., Cancio, M., Nadler, J. P., Chaitt, D. G., Dewar, R. L., Sahner, D. K., Duliege, A.-M., Capra, W. B., Leong, W.-P., Giedlin, M. A., Lane, H. C., Kahn, J. O. (2000). Immunologic and Virologic Effects of Subcutaneous Interleukin 2 in Combination With Antiretroviral Therapy: A Randomized Controlled Trial. JAMA 284: 183-189 [Abstract] [Full Text]  
• Blankson, J., Siliciano, R. F. (2000). Interleukin 2 Treatment for HIV Infection. JAMA 284: 236-238 [Full Text]  
• Pedersen, B. K., Hoffman-Goetz, L. (2000). Exercise and the Immune System: Regulation, Integration, and Adaptation. Physiol. Rev. 80: 1055-1081 [Abstract] [Full Text]  
• Campbell, T. B., Sevin, A., Coombs, R. W., Peterson, G. C., Rosandich, M., Kuritzkes, D. R., Mladenovic, J., Landay, A., Wong, R., Ambruso, D., Miles, S., Pomerantz, R. J., Schooley, R. T., the Adult AIDS Clinical Trials Group 285 Study Tea, (2000). Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells. Blood 95: 48-55 [Abstract] [Full Text]  
• Ferguson, N. M., deWolf, F., Ghani, A. C., Fraser, C., Donnelly, C. A., Reiss, P., Lange, J. M. A., Danner, S. A., Garnett, G. P., Goudsmit, J., Anderson, R. M. (1999). Antigen-driven CD4+ T cell and HIV-1 dynamics: Residual viral replication under highly active antiretroviral therapy. Proc. Natl. Acad. Sci. USA 96: 15167-15172 [Abstract] [Full Text]  
• Bovolenta, C., Camorali, L., Lorini, A. L., Vallanti, G., Ghezzi, S., Tambussi, G., Lazzarin, A., Poli, G. (1999). In Vivo Administration of Recombinant IL-2 to Individuals Infected by HIV Down-Modulates the Binding and Expression of the Transcription Factors Ying-Yang-1 and Leader Binding Protein-1/Late Simian Virus 40 Factor. J. Immunol. 163: 6892-6897 [Abstract] [Full Text]  
• Chun, T.-W., Fauci, A. S. (1999). Latent reservoirs of HIV: Obstacles to the eradication of virus. Proc. Natl. Acad. Sci. USA 96: 10958-10961 [Full Text]  
• Greenberg, P. D., Riddell, S. R. (1999). Deficient Cellular Immunity--Finding and Fixing the Defects. Science 285: 546-551 [Abstract] [Full Text]  
• Achour, A., Landureau, J.-C., Salerno-Concalves, R., Mazière, J.-C., Zagury, D. (1998). Restoration of Immune Response by a Cationic Amphiphilic Drug (AY 9944) In Vitro: A New Approach To Chemotherapy against Human Immunodeficiency Virus Type 1. Antimicrob. Agents Chemother. 42: 2482-2491 [Abstract] [Full Text]  
• Parada, N. A., Center, D. M., Kornfeld, H., Rodriguez, W. L., Cook, J., Vallen, M., Cruikshank, W. W. (1998). Synergistic Activation of CD4+ T Cells by IL-16 and IL-2. J. Immunol. 160: 2115-2120 [Abstract] [Full Text]  
• Trimble, L. A., Lieberman, J. (1998). Circulating CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Individuals Have Impaired Function and Downmodulate CD3zeta , the Signaling Chain of the T-Cell Receptor Complex. Blood 91: 585-594 [Abstract] [Full Text]  
• QUEZADO, Z. M. N., KARZAI, W., DANNER, R. L., FREEMAN, B. D., YAN, L., EICHACKER, P. Q., BANKS, S. M., PERREN COBB, J., CUNNION, R. E., QUEZADO, M. J. N., SEVRANSKY, J. E., NATANSON, C. (1997). Effects of L-NMMA and Fluid Loading on TNF-induced Cardiovascular Dysfunction in Dogs. Am. J. Respir. Crit. Care Med. 157: 1397-1405 [Abstract] [Full Text]  
• Jacobson, E. L., Pilaro, F., Smith, K. A., Kovacs, J. A., Davey, R. T., Lane, H. C. (1997). Interleukin-2 Infusions in HIV-Infected Patients. NEJM 336: 1260-1261 [Full Text]  
• Kovacs, J. A., Vogel, S., Albert, J. M., Falloon, J., Davey, R. T., Walker, R. E., Polis, M. A., Spooner, K., Metcalf, J. A., Baseler, M., Fyfe, G., Lane, H. C., Dewar, R. J., Masur, H. (1996). Controlled Trial of Interleukin-2 Infusions in Patients Infected with the Human Immunodeficiency Virus. NEJM 335: 1350-1356 [Abstract] [Full Text]  
• Disla, E., Goldberg, B., Landonio, G., Baiocchi, C., Ferrari, M., Lane, H. C., Kovacs, J. A. (1995). Interleukin-2 as Therapy for HIV Disease. NEJM 333: 192-193 [Full Text]  
• (1995). Intermittent IL-2 Can Restore Immune Function if Given Early. AIDS Clin Care 1995: 6-6 [Full Text]  
• (1995). INTERLEUKIN-2 INCREASES CD4 COUNT IN HIV INFECTION. JWatch General 1995: 1-1 [Full Text]