Tributyltin exposure alters cytokine levels in mouse serum

Abstract

Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL2, IL5, IL7, IL12βp40, IL13, IL15, KC, MIP1β, MIP2 and RANTES was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1β, IL-2, IL5, IL12βp40, and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in serum of mice exposed to TBT for less than 24 hr. IL1-β, IL-12βp40, IL-5 and IL-15 were also modulated in mouse serum depending on the specific experiment and the exposure concentration. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1β, RANTES, and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

Tributyltin and Zebrafish: Swimming in Dangerous Water

“…Thus, TBT is an inducer of oxidative stress and plays an important role in the positive modulation of pro-inflammatory cytokines ( 45 ). This is consistent with data showing a decreased activity of SOD, CAT, and GPX in other species ( 46 , 47 ), a higher expression of HSP70 in common carp ( 48 ), an increased IL-1β secretion by human immune cells ( 49 ), an increased IL-6 production in human peripheral blood mononuclear cells ( 50 ), and higher TNF-α levels in mouse serum ( 51 ).…”

Environmental Health and Toxicology: Immunomodulation Promoted by Endocrine-Disrupting Chemical Tributyltin

“…In addition, BALB/c mice injected with 100 nM of TBT showed an increase in serum levels of the cytokines IFN-γ, TNF-α and IL-13 and the chemokines MIP-1β and RANTES. A decrease in the cytokine IL-2, which is essential for the maturation of B and T lymphocytes, was also observed [ 44 ]. In splenic cells of CBA/J mice stimulated in vitro with anti-mouse CD3 antibodies, exposure to 0.1 µM of TBT was sufficient to inhibit the secretion of IFN-γ and IL-4 by T CD4 cells [ 73 ].…”

“…The balance of synthesis and secretion (autocrine and paracrine signaling) of different cytokines by immune cells and other cell types, such as endothelial cells, fibroblasts and bone marrow cells, maintains the multicellular network of communication in the microenvironment [ 43 ]. In fact, cytokines are the basis of communication for the initiation, maintenance and termination of immune responses to infections, and any change in them can lead to extremes, such as immunosuppression or the establishment of chronic inflammation [ 44 ]. TNF-α, for example, modulates the function of effector immune cells, such as neutrophils, promoting an increase in their activity, adherence and chemotaxis.…”