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

Abstract

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.

Effect of Interleukin-1 Receptor Antagonist on Concanavalin A Response of Peripheral Blood Mononuclear Cells from Newborn Calves.

“…When peripheral blood mononuclear cells (PBMC) are stimulated with ConA, IL-1 is produced by monocytes present in the PBMC fraction. Therefore, ConA-stimulated PBMC proliferation is suppressed by IL-1ra [6]. Using this system, we investigated the effect of the simultaneous presence of IL-1β and IL-1ra on ConA response of PBMC from newborn calves before feeding colostrum.…”

Inhibition of concanavalin a‐induced proliferative responses of mouse spleen cells and rabbit Peyer's patch cells by hen egg‐white avidin

“…Ruscetti et al (1992), however, reported that transforming growth factors TGF-/J1 and TGF-/J2 inhibited mitogen-induced T-lymphocyte proliferation. Moreover, Conti et al (1991) reported that the optimal mitogenic effect of Con A was inhibited by an interleukin-1 (IL-1) receptor antagonist. These facts suggested that hen egg-white avidin suppressed the formation of a cytokine required for the Con A-induced proliferative response of mouse spleen cells, or induced the production of a cytokine or cytokine antagonist which inhibited the Con A-induced proliferation.…”

Recombinant Human Granulocyte Colony-Stimulating Factor (rHuG-CSF): Effects on Lymphocyte Phenotype and Function

“…(50)(51)(52)(53) Similarly, IL-1ra may exert a dose-response inhibition of lymphocyte mitogenesis. (54) …”