Effects of imipenem and cilastatin on human T-lymphocytes derived from acute leukemia patients with chemotherapy-induced leucopenia: studies of T-lymphocyte responses in the presence of acute myelogenous leukemia (AML) blast accessory cells.
The effects of imipenem and cilastatin on human T-lymphocytes were studied in vitro. As responder T-cells were used T-lymphocyte clones derived from acute leukemia patients with chemotherapy-induced cytopenia, and the accessory cells were highly enriched acute myelogenous leukemia (AML) blasts. The effects of imipenem and cilastatin on phytohemagglutinin (PHA), anti-CD3 and anti-CD3+anti-CD28 stimulated activation were assayed, and in addition drug effects on cytokine-dependent proliferation of activated T-lymphocytes were investigated. Imipenem inhibited IL2-dependent proliferation of activated CD4(+) and CD8(+) T-cell clones, and an inhibition was also detected for IL7-, IL12-, IL15-, IL16- and IL17-dependent clonal proliferation. Imipenem caused a weak inhibition of anti-CD3- and PHA-stimulated T-cell proliferation when using 50 Gy irradiated AML blast accessory cells derived from various patients, whereas no effect was observed for anti-CD3+anti-CD28 stimulated and allostimulated activation. Imipenem decreased the release of IL4 and Interferon-gamma by T-cell clones stimulated with anti-CD3 and PHA in the presence of native (nonirradiated) AML blasts. The imipenem effects were observed at concentrations corresponding to levels reached in vivo, whereas even high concentrations of cilastatin did not alter T-cell responses. The T-lymphocyte inhibition is probably caused by a direct effect of imipenem on the T-cells.
Bruserud
O
O
Division for Hematology, Department of Medicine, Haukeland University Hospital and the University of Bergen, Bergen, Norway.
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015377:Cilastatin / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D007970:Leukopenia / Q000139:chemically induced / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects*
D000970:Antineoplastic Agents; D016207:Cytokines; D007376:Interleukin-2; D015377:Cilastatin; D015378:Imipenem