Differential reconstitution of zidovudine-induced inhibition of mitogenic responses by interleukin-2 in peripheral blood mononuclear cells from patients with human immunodeficiency virus infection

Mostafa A. Nokta, Richard B Pollard

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Zidovudine (ZDV), an anti-human immunodeficiency virus (HIV) therapy, has been associated with reduction in mortality and improvement of patients with acquired immunodeficiency syndrome (AIDS). The ZDV recipients, however, experience a multitude of side effects of which bone marrow suppression is the most noteworthy, especially among patients with low CD4 cell counts. The effect of ZDV and interleukin-2 (IL-2) on phytohemagglutinin (PHA)-induced proliferative response of peripheral blood mononuclear cells (PBMs) from patients with HIV infection was investigated. ZDV 0.5 μg inhibited 40% of PHA-induced thymidine uptake in PBMs from healthy donors or patients with HIV, irrespective of their CD4 cell counts. However, IL-2 (10 U/ml) had differential effect on PHA-induced thymidine uptake that appeared to be dependent on absolute CD4 cell counts. While PBMs from patients with CD4 cell counts of 400/mm3 or more did not respond to IL-2 (low responders), IL-2 enhanced the PHA-induced thymidine uptake in PBMs from patients with CD4 cell counts less than 400/mm3 at an average of 60% (high responders). Moreover, IL-2 restored the ZDV-induced inhibition by almost 100% in the high responder group while it did not affect counts in the low responder group. The production of IL-2 in vitro, in response to PHA or recall antigens, was equivalently inhibited in both groups. These data suggest that ZDV and IL-2 could have an additive effect on immune parameters in certain groups of patients infected with HIV. The differential effect of IL-2 was independent of IL-2 receptor expression.

Original languageEnglish (US)
Pages (from-to)191-202
Number of pages12
JournalAntiviral Research
Volume11
Issue number4
DOIs
StatePublished - 1989
Externally publishedYes

Fingerprint

Zidovudine
Virus Diseases
Interleukin-2
Blood Cells
HIV
Phytohemagglutinins
CD4 Lymphocyte Count
Thymidine
Interleukin-2 Receptors
Interleukin-10
Acquired Immunodeficiency Syndrome
Bone Marrow
Tissue Donors
Antigens
Mortality
phytobacteriomycin

Keywords

  • AIDS
  • HIV
  • IL-2
  • ZDV

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

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title = "Differential reconstitution of zidovudine-induced inhibition of mitogenic responses by interleukin-2 in peripheral blood mononuclear cells from patients with human immunodeficiency virus infection",
abstract = "Zidovudine (ZDV), an anti-human immunodeficiency virus (HIV) therapy, has been associated with reduction in mortality and improvement of patients with acquired immunodeficiency syndrome (AIDS). The ZDV recipients, however, experience a multitude of side effects of which bone marrow suppression is the most noteworthy, especially among patients with low CD4 cell counts. The effect of ZDV and interleukin-2 (IL-2) on phytohemagglutinin (PHA)-induced proliferative response of peripheral blood mononuclear cells (PBMs) from patients with HIV infection was investigated. ZDV 0.5 μg inhibited 40{\%} of PHA-induced thymidine uptake in PBMs from healthy donors or patients with HIV, irrespective of their CD4 cell counts. However, IL-2 (10 U/ml) had differential effect on PHA-induced thymidine uptake that appeared to be dependent on absolute CD4 cell counts. While PBMs from patients with CD4 cell counts of 400/mm3 or more did not respond to IL-2 (low responders), IL-2 enhanced the PHA-induced thymidine uptake in PBMs from patients with CD4 cell counts less than 400/mm3 at an average of 60{\%} (high responders). Moreover, IL-2 restored the ZDV-induced inhibition by almost 100{\%} in the high responder group while it did not affect counts in the low responder group. The production of IL-2 in vitro, in response to PHA or recall antigens, was equivalently inhibited in both groups. These data suggest that ZDV and IL-2 could have an additive effect on immune parameters in certain groups of patients infected with HIV. The differential effect of IL-2 was independent of IL-2 receptor expression.",
keywords = "AIDS, HIV, IL-2, ZDV",
author = "Nokta, {Mostafa A.} and Pollard, {Richard B}",
year = "1989",
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language = "English (US)",
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T1 - Differential reconstitution of zidovudine-induced inhibition of mitogenic responses by interleukin-2 in peripheral blood mononuclear cells from patients with human immunodeficiency virus infection

AU - Nokta, Mostafa A.

AU - Pollard, Richard B

PY - 1989

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N2 - Zidovudine (ZDV), an anti-human immunodeficiency virus (HIV) therapy, has been associated with reduction in mortality and improvement of patients with acquired immunodeficiency syndrome (AIDS). The ZDV recipients, however, experience a multitude of side effects of which bone marrow suppression is the most noteworthy, especially among patients with low CD4 cell counts. The effect of ZDV and interleukin-2 (IL-2) on phytohemagglutinin (PHA)-induced proliferative response of peripheral blood mononuclear cells (PBMs) from patients with HIV infection was investigated. ZDV 0.5 μg inhibited 40% of PHA-induced thymidine uptake in PBMs from healthy donors or patients with HIV, irrespective of their CD4 cell counts. However, IL-2 (10 U/ml) had differential effect on PHA-induced thymidine uptake that appeared to be dependent on absolute CD4 cell counts. While PBMs from patients with CD4 cell counts of 400/mm3 or more did not respond to IL-2 (low responders), IL-2 enhanced the PHA-induced thymidine uptake in PBMs from patients with CD4 cell counts less than 400/mm3 at an average of 60% (high responders). Moreover, IL-2 restored the ZDV-induced inhibition by almost 100% in the high responder group while it did not affect counts in the low responder group. The production of IL-2 in vitro, in response to PHA or recall antigens, was equivalently inhibited in both groups. These data suggest that ZDV and IL-2 could have an additive effect on immune parameters in certain groups of patients infected with HIV. The differential effect of IL-2 was independent of IL-2 receptor expression.

AB - Zidovudine (ZDV), an anti-human immunodeficiency virus (HIV) therapy, has been associated with reduction in mortality and improvement of patients with acquired immunodeficiency syndrome (AIDS). The ZDV recipients, however, experience a multitude of side effects of which bone marrow suppression is the most noteworthy, especially among patients with low CD4 cell counts. The effect of ZDV and interleukin-2 (IL-2) on phytohemagglutinin (PHA)-induced proliferative response of peripheral blood mononuclear cells (PBMs) from patients with HIV infection was investigated. ZDV 0.5 μg inhibited 40% of PHA-induced thymidine uptake in PBMs from healthy donors or patients with HIV, irrespective of their CD4 cell counts. However, IL-2 (10 U/ml) had differential effect on PHA-induced thymidine uptake that appeared to be dependent on absolute CD4 cell counts. While PBMs from patients with CD4 cell counts of 400/mm3 or more did not respond to IL-2 (low responders), IL-2 enhanced the PHA-induced thymidine uptake in PBMs from patients with CD4 cell counts less than 400/mm3 at an average of 60% (high responders). Moreover, IL-2 restored the ZDV-induced inhibition by almost 100% in the high responder group while it did not affect counts in the low responder group. The production of IL-2 in vitro, in response to PHA or recall antigens, was equivalently inhibited in both groups. These data suggest that ZDV and IL-2 could have an additive effect on immune parameters in certain groups of patients infected with HIV. The differential effect of IL-2 was independent of IL-2 receptor expression.

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