Differential reconstitution of zidovudine-induced inhibition of mitogenic responses by interleukin-2 in peripheral blood mononuclear cells from patients with human immunodeficiency virus infection.
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 micrograms 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.
Nokta
M A
MA
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Pollard
R B
RB
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016827:CD8 Antigens; D002478:Cells, Cultured; D003586:Cytomegalovirus Infections / Q000276:immunology; D004261:DNA Replication / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects; D012016:Reference Values; D015215:Zidovudine / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D015215:Zidovudine