Abstract
Roquinimex (Roq) is an immunomodulator known to stimulate cellular immune responses. It is currently used for immunotherapy after bone marrow transplantation (BMT). One of the major features of this compound is an enhancement of natural killer (NK) cell activity and numbers. We studied the in vitro effect of Roq on human peripheral blood NK and adherent lymphokine-activated killer cell (ALAK) activities. In cultures supplemented with recombinant interleukin 2 (rIL-2) (1000 U ml-1) and Roq a significant increase in NK and LAK function was observed without a parallel increase in cell numbers. We also examined the generation of NK cells from human bone marrow (BM) immature progenitors, obtained by purging with 4-hydroperoxycyclophosphamide (4HC). NK cell numbers and activity were both increased when cultures with rIL-2 (10 U ml-1) were supplemented with Roq. These results confirm findings obtained in vivo and in vitro in the murine system and suggest that Roq is an active agent on these lymphoid populations. These properties and good tolerability make Roq an attractive tool for immunotherapy.
Highlights
We suggest that Roq is active in vitro in stimulating natural killer (NK) and LAK activity in mature peripheral blood cells; at the precursor cell level Roq is capable of increasing NK cell numbers and activity
Cultures only supplemented with recombinant interleukin 2 (rIL-2) had the highest proliferation rate (6.0 ± 1.1) as compared with the control
By comparison, when Roq was added to rIL-2 the difference in cell expansion was not statistically significant (P = 0.3 for rIL-2 plus Roq 50 jig ml-' and P=0.1 for rIL-2 and Roq 25 1ig ml-')
Summary
ReagentsRoquinimex is a quinoline-3-carboxamide, its tradename is Linomide (Pharmacia Lund, Sweden).Production of ALAK cellsPeripheral blood was obtained from healthy donors after informed consent was given. Peripheral blood mononuclear cells (PBMNCs) obtained by Ficoll Hypaque (Histopaque; Sigma Diagnostics, St Louis, MO, USA) depleted of monocytes by plastic adherence were suspended in culture medium containing. Culture medium used for rIL-2 incubations consisted of Iscoves's modified Dulbecco medium (IMDM) (Gibco, Grand Island, NY, USA) supplemented with 10% human heat-inactivated AB male serum After 24 h incubation, the supernatant was decanted and all cells not firmly attached to the plastic were removed by washing three times with IMDM. The plastic adherent (ALAK) cells were fed with fresh media supplemented with rIL-2 (1000 U ml-'), Roq (25 lig ml-' or 50 tLg ml-') or combinations for up to 14 days. At termination of culture cells were recovered by washing the flasks with cold IMDM or with phosphate-buffered saline (PBS) containing 0.01 M EDTA
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