Abstract
The cytokine interleukin-10 (IL-10) has been implicated in the pathogenesis of a number of disease states, including Epstein-Barr virus and human immunodeficiency virus (HIV-1) infections. In the acquired immunodeficiency syndrome (AIDS), it has been suggested that IL-10 may have a deleterious effect by suppressing cell-mediated immunity. However, there are few data on its direct effects on HIV-1 replication. In the present study, we have found that recombinant human IL-10 (rhIL-10), present during days 0 through 2, potently inhibits HIV production in elutriated monocyte/macrophage (M/M) cultures with a 50% inhibitory concentration (IC 50) of approximately 0.03 U/mL. This effect did not appear to be caused by toxicity to M/M because there was no change in cell viability, ability to phagocytose latex beads, or protein synthesis as measured by [ 3H]-leucine incorporation, at doses of rhIL-10 that inhibit viral replication. In addition, lipopolysaccharide- induced production of IL-1β, IL-6, or tumor necrosis factor-α was not affected at these doses, nor were human mononuclear cell proliferative responses to phytohemagglutinin, OKT3 antibody, or tetanus toxoid. HIV-1 replication was similarly decreased by rhIL-10 in the monocytoid line U937 without signs of cellular toxicity. However, these effects required much higher concentrations or rhIL-10, and viral production was only partially suppressed. rhIL-10 also slightly inhibited HIV-induced cytopathicity in ATH- 8, a tetanus toxoid-specific, retrovirally immortalized T-cell line, but had no effect on HIV replication in the H9 and MOLT-4 T cell lines. Thus, rhIL- 10 appears to inhibit HIV replication predominantly in cells of the M/M lineage. This effect may serve to reduce viral production in patients with AIDS. However, additional studies will be needed to more precisely define its physiologic role in this disease.
| Original language | English |
|---|---|
| Pages (from-to) | 3591-3599 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 83 |
| Issue number | 12 |
| Publication status | Published - Jun 15 1994 |
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ASJC Scopus subject areas
- Hematology
Cite this
Interleukin-10 suppresses human immunodeficiency virus-1 replication in vitro in cells of the monocyte/macrophage lineage. / Saville, M. Wayne; Taga, Kazayuki; Foli, Andrea; Broder, Samuel; Tosato, Giovanna; Yarchoan, Robert.
In: Blood, Vol. 83, No. 12, 15.06.1994, p. 3591-3599.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interleukin-10 suppresses human immunodeficiency virus-1 replication in vitro in cells of the monocyte/macrophage lineage
AU - Saville, M. Wayne
AU - Taga, Kazayuki
AU - Foli, Andrea
AU - Broder, Samuel
AU - Tosato, Giovanna
AU - Yarchoan, Robert
PY - 1994/6/15
Y1 - 1994/6/15
N2 - The cytokine interleukin-10 (IL-10) has been implicated in the pathogenesis of a number of disease states, including Epstein-Barr virus and human immunodeficiency virus (HIV-1) infections. In the acquired immunodeficiency syndrome (AIDS), it has been suggested that IL-10 may have a deleterious effect by suppressing cell-mediated immunity. However, there are few data on its direct effects on HIV-1 replication. In the present study, we have found that recombinant human IL-10 (rhIL-10), present during days 0 through 2, potently inhibits HIV production in elutriated monocyte/macrophage (M/M) cultures with a 50% inhibitory concentration (IC 50) of approximately 0.03 U/mL. This effect did not appear to be caused by toxicity to M/M because there was no change in cell viability, ability to phagocytose latex beads, or protein synthesis as measured by [ 3H]-leucine incorporation, at doses of rhIL-10 that inhibit viral replication. In addition, lipopolysaccharide- induced production of IL-1β, IL-6, or tumor necrosis factor-α was not affected at these doses, nor were human mononuclear cell proliferative responses to phytohemagglutinin, OKT3 antibody, or tetanus toxoid. HIV-1 replication was similarly decreased by rhIL-10 in the monocytoid line U937 without signs of cellular toxicity. However, these effects required much higher concentrations or rhIL-10, and viral production was only partially suppressed. rhIL-10 also slightly inhibited HIV-induced cytopathicity in ATH- 8, a tetanus toxoid-specific, retrovirally immortalized T-cell line, but had no effect on HIV replication in the H9 and MOLT-4 T cell lines. Thus, rhIL- 10 appears to inhibit HIV replication predominantly in cells of the M/M lineage. This effect may serve to reduce viral production in patients with AIDS. However, additional studies will be needed to more precisely define its physiologic role in this disease.
AB - The cytokine interleukin-10 (IL-10) has been implicated in the pathogenesis of a number of disease states, including Epstein-Barr virus and human immunodeficiency virus (HIV-1) infections. In the acquired immunodeficiency syndrome (AIDS), it has been suggested that IL-10 may have a deleterious effect by suppressing cell-mediated immunity. However, there are few data on its direct effects on HIV-1 replication. In the present study, we have found that recombinant human IL-10 (rhIL-10), present during days 0 through 2, potently inhibits HIV production in elutriated monocyte/macrophage (M/M) cultures with a 50% inhibitory concentration (IC 50) of approximately 0.03 U/mL. This effect did not appear to be caused by toxicity to M/M because there was no change in cell viability, ability to phagocytose latex beads, or protein synthesis as measured by [ 3H]-leucine incorporation, at doses of rhIL-10 that inhibit viral replication. In addition, lipopolysaccharide- induced production of IL-1β, IL-6, or tumor necrosis factor-α was not affected at these doses, nor were human mononuclear cell proliferative responses to phytohemagglutinin, OKT3 antibody, or tetanus toxoid. HIV-1 replication was similarly decreased by rhIL-10 in the monocytoid line U937 without signs of cellular toxicity. However, these effects required much higher concentrations or rhIL-10, and viral production was only partially suppressed. rhIL-10 also slightly inhibited HIV-induced cytopathicity in ATH- 8, a tetanus toxoid-specific, retrovirally immortalized T-cell line, but had no effect on HIV replication in the H9 and MOLT-4 T cell lines. Thus, rhIL- 10 appears to inhibit HIV replication predominantly in cells of the M/M lineage. This effect may serve to reduce viral production in patients with AIDS. However, additional studies will be needed to more precisely define its physiologic role in this disease.
UR - http://www.scopus.com/inward/record.url?scp=0028340875&partnerID=8YFLogxK
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M3 - Article
C2 - 7911340
AN - SCOPUS:0028340875
VL - 83
SP - 3591
EP - 3599
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -