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Recombinant human interleukin‐4 inhibits the production of granulocyte‐macrophage colony stimulating factor by blood mononuclear cells
Author(s) -
Sato Norihiro,
Sawada Kenichi,
Tarumi Takashi,
Koizumi Kazuki,
Yasukouchi Taro,
Takahashi Tsuneo A.,
Sekiguchi Sadayoshi,
Koike Takao
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb04817.x
Subject(s) - peripheral blood mononuclear cell , granulocyte macrophage colony stimulating factor , microbiology and biotechnology , cytokine , recombinant dna , granulocyte , interleukin , interleukin 3 , chemistry , biology , endocrinology , medicine , immunology , in vitro , biochemistry , t cell , immune system , interleukin 21 , gene
Summary. The effect of recombinant human (rh) interleukin‐4 (rIL‐4) on human blood BFU‐E was investigated using two populations of cells: platelet‐depleted low‐density mononuclear cells (FH, Pl − cells), as unpurified cells, and highly purified BFU‐E. When FH, Pl − cells were cultured with rherythropoietin (rEp), rIL‐4 inhibited BFU‐E growth in a dose‐dependent manner. However, the addition of rIL‐4 did not affect rh‐interleukin‐3 (rIL‐3) supported BFU‐E growth. Limiting dilution analysis (LDA) of FH, Pl − cells showed that rIL‐4 suppressed endogenous production of burst‐promoting activity (BPA) by accessory cells. Highly purified BFU‐E were used as target cells to measure BPA in the conditioned medium (CM) that was prepared by FH, Pl − cells. When 100 purified BFU‐E were cultured in 0·5 ml clots with 20% (vol/vol) of the CM, the number of BFU‐E colonies was increased by the CM. The increase was significantly reduced by the addition of the CM prepared in the presence of rIL‐4, but anti‐IL‐4 blocked the effect of rIL‐4. The concentration of IL‐3 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in CM was determined by an enzyme‐linked immunoadsorbent assay (ELISA). The spontaneous production of GM‐CSF but not IL‐3 was detected, and this was significantly decreased in the presence of rIL‐4. Anti‐GM‐CSF but not anti‐IL‐3 inhibited CM supported BFU‐E growth, indicating that the main BPA in the CM is GM‐CSF and that rIL‐4 suppresses the spontaneous production of GM‐CSF by accessory cells. From these studies, we conclude that rIL‐4 has a unique mechanism as a negative regulator on erythropoiesis through the inhibition of BPA production by blood mononuclear accessory cells.