Human recombinant interleukin‐1 receptor antagonist inhibits lymphocyte blastogenesis induced by concanavalin A Restorative effect of hrIL‐1

FEBS Letters

Panara, Maria R.³  Reale, Marcella¹  Barbacane, Renato C.¹  Conti, Pio¹  Dempsey, Roy A.²  Bongrazio, Mauro³ 

[1] Immunology Division, Institute of Experimental Medicine, University of Chieti, 66100 Chieti, Italy;Cytokine Research Laboratory, Endogen, Inc., Boston, MA 02111, USA;Institute of Normal and Pathologic Cytomorphology, CNR, University of Chieti, 66100 Chieti, Italy

关键词: Interleukin-1 receptor antagonist;    Concanavalin A;    Lymphocyte;    Blastogenesis;    Interleukin;    T-cell;    hrIL-1ra;    human recombinant interleukin-1 receptor antagonist;    hrIL-1;    human recombinant interleukin-1;    IL-2;    interleukin-2;    Con A;    concanavalin A;    PBMC;    peripheral blood mononuclear cells;    3H-TdR;    [methyl-3H]thymidine;   

DOI  :  10.1016/0014-5793(91)80959-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Interleukin-1 (IL-1), mainly produced by monocyte-macrophages, is a polypeptide cytokine with pleiotropic biological effects. IL-1 plays an important role in mediating immune response and inflammation. Recently a natural inhibitor to IL-1 has been discovered, interleukin-1 receptor antagonist (IL-1ra), produced by human monocytes cultured on adherent IgG which binds to the IL-1 receptors. In our study we found that the pretreatment of cells with serial dilutions of IL-1ra (250 ng/ml−2.5 pg/ml) inhibits, in a dose-dependent manner, lymphocyte DNA synthesis stimulated with Con A (10 μg/ml). IL-1ra did not have any effect on resting peripheral blood mononuclear cells (PBMC). Time course experiments show that IL-1ra at 250 ng/ml has its maximum inhibitory effect on lymphocyte blastogenesis when cells are pretreated 2 h before Con A. No effect was found when hrIL-1ra was added after Con A. Moreover, hrIL-1ra also inhibits the enhancing effects of exogenous hrIL-1 (400, 200, 100 and 50 ng/ml) on lymphocytes stimulated with Con A; while when hrIL-1ra was used on cells treated with only Con A, the inhibition was more pronounced. When PBMC were removed from monocytes, by adherence, the Con A-treated lymphocytes were not influenced by 2 h pretreatment of hrIL-1ra; while a strong inhibition was found when exogenous hrIL-1 was added at different concentrations. In addition, hrIL-1ra also inhibits the enhancing effect of hrIL-2 on lymphocyte DNA synthesis. In another set of experiments PBMC were pretreated with hrIL-1ra (250 ng/ml) for 2 h and then added LPs (10 ng/ml) and IL-1α generation was determined using ELISA. In these experiments IL-1ra completely abolished the generation of IL-1α. These data suggest that hrIL-1ra exhibits a dose—response inhibition of lymphocyte blastogenesis induced by Con A, probably through the down-regulation of IL-1 synthesis necessary as an early signal for T-cell activation and IL-2 production.

【 授权许可】

Unknown