title: Antiproliferative effect of interleukin-4 in B chronic lymphocytic leukemia.
abstract: Recombinant interleukin-4 (IL-4) profoundly inhibits the proliferative response of chronic lymphocytic leukemic B cells (B-CLLs) to recombinant interleukin-2 (IL-2). In the present study, we confirmed and extended these data by showing that IL-4 strongly suppresses the [3H]thymidine incorporation by B-CLLs stimulated by recombinant tumor necrosis factor alpha, recombinant interferon alpha, IL-2, and low molecular weight B cell growth factor in the absence of costimulant. Recombinant interleukin-4 inhibits spontaneous DNA synthesis suggesting that it also interferes with the autocrine proliferation of these cells. Kinetic studies indicate that IL-4 suppresses rather than shifts the peak of cytokine-induced DNA synthesis. Moreover, IL-4 blocks the progression of B-CLLs in or into G1 stage of the cell cycle as shown by the inhibition of cytokine-induced [3H]uridine incorporation. Finally, IL-4 pretreatment of B-CLLs prevents their subsequent proliferative response to the above cytokines, indicating that IL-4 confers to the B-CLLs a state of resistance to numerous stimulatory cytokines. The antiproliferative effects of IL-4 suggest that this lymphokine may have important therapeutic implications for the B-CLL patients.
authors.affiliation: Notre Dame Hospital Research Centre, University of Montreal, Quebec, Canada.
authors.forename: H Y
authors.initials: HY
authors.lastname: Luo
authors.forename: M
authors.initials: M
authors.lastname: Rubio
authors.forename: G
authors.initials: G
authors.lastname: Biron
authors.forename: G
authors.initials: G
authors.lastname: Delespesse
authors.forename: M
authors.initials: M
authors.lastname: Sarfati
mesh_terms: D002453:Cell Cycle; D002455:Cell Division; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004273:DNA, Neoplasm; D016898:Interferon-alpha; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4