Dibutyltin alters immune cell production of the pro-inflammatory cytokines interleukin (IL) 1β and IL-6: role of mitogen-activated protein kinases and changes in mRNA.

Dibutyltin (DBT) is used to stabilize plastics and as a deworming agent in some poultry. It is found in human blood (levels as high as 0.3 μM). Interleukin (IL) 1β (IL-1β) and IL-6 are pro-inflammatory cytokines produced by lymphocytes, monocytes, and other cells. Elevated levels of IL-1β and IL-6 have been associated with pathologies including rheumatoid arthritis and cancers. DBT was shown to decrease IL-1β and IL-6 secretion from immune cells at higher concentrations while causing increases at lower concentrations. However, it was not clear if these changes were due to DBT's alteration of the secretory process or due its ability to change cellular synthesis/production of these proteins. This study addresses this question, as well as mechanisms for any observed changes in synthesis/production. Monocyte-depleted peripheral blood mononuclear cells (MD-PBMCs) were exposed to DBT at concentrations of 5, 2.5, 1, 0.5, 0.25, 0.1, and 0.05 μM for 1, 6, and 24 h and the production (combination of secreted and intracellular levels from the same cells) of both IL-1β and IL-6 were measured. Effects of selected DBT exposures on cytokine production were also examined in PBMCs and DBT's effects were similar when monocytes were present. The 24-h exposures to DBT decreased production of both IL-1β and IL-6 at the two highest concentrations but increased production at lower concentrations. Both decreases and increases in cytokine production appear to be explained by DBT-induced changes in mRNA levels. DBT-induced increases in cellular production of the cytokines appear to require p38 and ERK1/2 MAPK pathways.