Inhibition of human T lymphoblast proliferation by hydroquinone.
Hydroquinone (HQ) is a major metabolite of benzene and is present in large quantities in cigarette tar as a result of the combustion of tobacco leaf pigments. We hypothesize that the immunosuppressive effects of cigarette smoking are due, in part, to the deposition of large quantities of HQ in the lungs. Exposure of primary human T lymphoblasts (HTL) in vitro to 50 microM HQ blocked IL-2-dependent proliferation by > 90% with no loss in viability. Inhibition of DNA synthesis was observed immediately after the addition of HQ to the cells. However, this effect could be reversed up to 6 hr later by simply washing the cells and reculturing them in the absence of HQ. HQ did not significantly alter intracellular glutathione levels up to 24 hr later, and the presence of 50 microM 2-mercaptoethanol or 500 microM dithiothreitol during the treatment did not prevent inhibition of DNA synthesis. HQ did not block binding of 125I-IL-2 to the cells, but inhibited the IL-2-dependent progression of HTL through S phase of the cell cycle. These observations demonstrate that HQ, in concentrations comparable to those found in cigarette tar, is a potent inhibitor of IL-2-dependent T cell proliferation and may therefore help to explain the potent immunosuppressive effects of cigarette smoke on lung T lymphocytes.
Li
Q
Q
Transplantation Immunology and HLA Laboratory, Albany Medical College, New York 12208, USA.
Geiselhart
L
L
Mittler
J N
JN
Mudzinski
S P
SP
Lawrence
D A
DA
Freed
B M
BM
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism / Q000633:toxicity*; D007108:Immune Tolerance / Q000187:drug effects*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000502:physiology; D016196:S Phase / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D006873:Hydroquinones; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; C031927:hydroquinone