Abstract
Tributyltin (TBT) is a widespread environmental contaminant that is present in human blood and other tissues. It has been shown to disrupt the immune function of human natural killer (NK) cells and to alter the secretion of a number of pro-inflammatory cytokines from immune cells. Secretion of both interleukin 1β (IL-1β) and interleukin 6 (IL-6) from human lymphocytes can be increased dependent upon the level of TBT exposure. This study shows that the TBT-induced increases in secretion of both cytokines are due to TBT-induced increases in the synthesis of these proteins and not simply because of the release of pre-existing cytokine. Furthermore, the data indicate that these TBT-induced increases in IL-1β and IL-6 synthesis require MAP kinase signaling pathways. Additionally, elevated synthesis of IL-1β and IL-6 seen at the highest exposures to TBT (200, 200, 50 nM) were accompanied by increases in the mRNA for these cytokines. TBT-induced increases in IL-1β and IL-6 mRNAs were also shown to be dependent on MAP kinase signaling. The study suggests that TBT has the capacity to increase immune cell production of these 2 important pro-inflammatory cytokines and that this increase is in part explained by increased mRNA for the cytokines.