Macrophage Secretory Function Is Enhanced by Low Doses of Tributyltin-Oxide (TBTO), But Not Tributyltin-Chloride (TBTCl)

Abstract.

Numerous studies suggest that tributyltin (TBT) is a potent immunotoxicant in nontarget organisms with lymphoid atrophy being a hallmark response. Two of the most common formulations of TBT are bis (tri-n-butyl)-tin oxide (TBTO) and tri-n-butyl-tin chloride (TBTCl). Most of studies investigating TBT-related immunotoxicity have used relatively high doses of both compounds, but little is known about the effects of very low doses. In addition, no studies have directly compared the effects of both formulations on immune function(s). We exposed female B6C3F1 mice to a single dose of TBTO or TBTCl at 0.3, 3.0, 30 mM/kg or corn oil as a carrier control. Forty-eight h later mice received a 4% solution of thioglycolate intraperitoneally to elicit peritoneal macrophages. Ninety-six h later macrophages were harvested and stimulated with a mixture of gamma-interferon (IFN-γ) and lipopolysaccharide (LPS). Nitric oxide (NO), tumor necrosis factor-α (TNF-α), transforming growth factor beta-1 (TGF-β₁), and phorbol ester-stimulated oxidative burst activity were then measured. Nitric oxide and TNF-α production were significantly elevated in the 0.3 and 3.0 mM TBTO/kg–treated groups but not in those treated by TBTCl. Background TNF-α production (without stimulation) was also elevated at these two doses but suppressed in TBTCl-treated animals. Oxidative burst activity was elevated at 0.3 mM TBTO/kg but not by TBTCl. TGF-β₁ production was not altered by either treatment, nor were body wts and organ-body wt ratios. To further evaluate the difference between the effects of TBTO and TBTCl on macrophage function, the in vitro toxicity of the two was determined using elicited peritoneal macrophages from untreated mice. Following a 24-h exposure to increasing concentrations of TBTO or TBTCl, functional viability was evaluated using the MTT assay. There were no differences between the two compounds in terms of treatment-related viability except that at the very highest concentrations (10⁻⁶ M) TBTO was more toxic than TBTCl.