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

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-i. Contra-IL-i 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-i 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-i did not inhibit IL-2-or IL4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-i did not interfere with the binding of recombinant IL-1i to a fibroblast cell line. Contra-IL-i 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,B. No message was apparent, suggesting that the presence of contra-IL-i was not obscuring the concomitant release of

Purification and characterization of a 26‐kDa competitive inhibitor of interleukin 1

“…Virus-infected monocytes/macrophages or monocytic cell lines have been shown to produce inhibitors of IL1. HIV-infected McP produce a 9-kDa inhibitor of IL 1 activity [27]. This inhibitor may be related to the urinary inhibitor of IL 1 described in this report.…”

“…Uromodulin, a 85-kDa glycoprotein isolated from the urine of pregnant women [35], has been cloned and shown to be identical to the Tamm-Horsfall glycoprotein [36,371. Uromodulin has been shown not to be a specific inhibitor of IL1 [38,39], but rather may act as a trap in the kidney for cytokines [37].The inhibitor found in cultures of HIV-infected MQ, has also been detected in the urine of AIDS patients [27]. It is interesting to note that the 26-kDa inhibitor of the present report is frequently found in the urine of AIDS patients.…”

HIV-1 Infection of Macrophages Promotes Long-Term Survival and Sustained Release of Interleukins lα and 6

“…The total area of neutralization of each monokine was calculated from graphs of the fractionation profiles as described in our previous studies. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] No TNF-a bioactivity was detectable in HIV-1-infected cultures assayed in the L-cell cytotoxicity assay on days 2 and 6 of incubation (data not shown). After 6 days of culture, selective increase in the release of IL-la and IL-6 bioactivity was evident in the HIV-1-infected macrophage cultures (lower panels, Fig.…”

HIV‐1‐infected and/or immune activated macrophages regulate astrocyte SDF‐1 production through IL‐1β

“…Elevated IL-1b has been demonstrated in CSF from patients infected with HIV-1 (Gallo et al, 1989). Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1b as examined by Northern analysis (Locksley et al, 1988). Brain tissue from HIV-1-seropositive individuals and HAD patients also showed higher IL-1b RNA expression as compared to seronegative controls (Suryadevara et al, 2003).…”