Advertisement

Research Article Free access | 10.1172/JCI113831

Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo.

R M Locksley, S Crowe, M D Sadick, F P Heinzel, K D Gardner Jr, M S McGrath, and J Mills

Department of Medicine, University of California San Francisco Medical Center 94143.

Find articles by Locksley, R. in: JCI | PubMed | Google Scholar

Department of Medicine, University of California San Francisco Medical Center 94143.

Find articles by Crowe, S. in: JCI | PubMed | Google Scholar

Department of Medicine, University of California San Francisco Medical Center 94143.

Find articles by Sadick, M. in: JCI | PubMed | Google Scholar

Department of Medicine, University of California San Francisco Medical Center 94143.

Find articles by Heinzel, F. in: JCI | PubMed | Google Scholar

Department of Medicine, University of California San Francisco Medical Center 94143.

Find articles by Gardner, K. in: JCI | PubMed | Google Scholar

Department of Medicine, University of California San Francisco Medical Center 94143.

Find articles by McGrath, M. in: JCI | PubMed | Google Scholar

Department of Medicine, University of California San Francisco Medical Center 94143.

Find articles by Mills, J. in: JCI | PubMed | Google Scholar

Published December 1, 1988 - More info

Published in Volume 82, Issue 6 on December 1, 1988
J Clin Invest. 1988;82(6):2097–2105. https://doi.org/10.1172/JCI113831.
© 1988 The American Society for Clinical Investigation
Published December 1, 1988 - Version history
View PDF
Abstract

Infection of monocyte-macrophages with human immunodeficiency virus may be central to the pathogenesis of the acquired immunodeficiency syndrome. The ability of infected macrophages to prime T cells through IL-1 production was investigated in vitro. Purified human monocytes maintained in suspension culture were infected with strain HIV-DV. Intracellular expression of virus p24 antigen increased from undetectable levels immediately after infection to 13-59% of cells by 10-14 d; infected macrophages remained viable for up to 60 d. Supernatants collected between 14 and 20 d after infection were examined in the murine thymocyte co-mitogenesis assay and demonstrated to contain a potent IL-1 inhibitor, designated contra-IL-1. Contra-IL-1 activity was present in all supernatants examined after 4 d of infection, and peaked coincident with peak p24 antigen expression. Inhibitory activity was not present in uninfected cells. Contra-IL-1 activity eluted after gel filtration with an approximate molecular weight of 9 kD. Inhibitory activity was removed by exposure to heat or acid pH, or by incubation with chymotrypsin or staphylococcal V8 protease. Contra-IL-1 did not inhibit IL-2- or IL-4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-1 did not interfere with the binding of recombinant IL-1 beta to a fibroblast cell line. Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1. Messenger RNA extracted from infected macrophages was examined by Northern analysis for the presence of message to IL-1 beta. No message was apparent, suggesting that the presence of contra-IL-1 was not obscuring the concomitant release of IL-1. Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1 beta. Spleen macrophages purified from two patients with AIDS complicated by immune thrombocytopenia spontaneously expressed p24 antigen in vitro and released contra-IL-1 activity into the media. Contra-IL-1 may contribute to the immune dysfunction of AIDS.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (December 1, 1988): No description
Advertisement
Advertisement