Butyltin compounds alter secretion of interleukin 6 from human immune cells

J Appl Toxicol. 2018 Feb;38(2):201-218. doi: 10.1002/jat.3514. Epub 2017 Aug 24.

Abstract

Butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT) are organotin compounds that have been used in a variety of industrial applications; as a result, these compounds have been found in human blood. Interleukin (IL)-6 is a proinflammatory mediator that is produced by T lymphocytes and monocytes. It is responsible for immune response regulation as well as tissue repair and cellular growth. Both BTs decrease the ability of human natural killer cells to destroy tumor cells and alter the secretion of proinflammatory cytokines tumor necrosis factor alpha, interferon gamma and IL-1 beta (β) from human lymphocytes ex vivo. Here, we show that BTs alter the secretion of IL-6 from increasingly reconstituted preparations of human immune cells. IL-6 secretion was examined after 24 hour, 48 hour or 6 day exposures to TBT and DBT in highly enriched human natural killer cells, monocyte-depleted peripheral blood mononuclear cells (PBMCs), PBMCs, granulocytes and a preparation combining both PBMCs and granulocytes (PBMCs + granulocytes). The results indicated that both BTs altered IL-6 secretion from all cell preparations. Significant decreases of IL-6 secretion were seen at the highest concentration of TBT (200 nm) and DBT (5-2.5 μm) while the lower concentrations of DBT (0.05 and 0.1 μm) caused elevation of IL-6 secretion. The data indicate that BT-induced alterations of IL-6 secretion from immune cells may be a significant consequence of BT exposures that may potentially affect immune competence.

Keywords: NK cells; PBMCs; dibutyltin; granulocytes; interleukin 6; tributyltin.

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Granulocytes / drug effects*
  • Granulocytes / immunology
  • Granulocytes / metabolism
  • Humans
  • Interleukin-6 / metabolism*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism
  • Organotin Compounds / toxicity*
  • Trialkyltin Compounds / toxicity*

Substances

  • Interleukin-6
  • Organotin Compounds
  • Trialkyltin Compounds
  • di-n-butyltin
  • tributyltin