Lifetime exposure to trichloroethylene (TCE) does not accelerate autoimmune disease in MRL +/+ mice

Abstract

A genetically-prone murine lupus model was used to assess the developmental effects of trichloroethylene (TCE) exposure on disease symptom onset (e.g., autoantibody production and proteinuria), lymphocyte proliferation, splenic B-cell populations, and thymic and splenic T-cell populations. MRL +/+ mice were exposed to TCE (0, 1,400 or 14,000 ppb) via drinking water beginning on gestation day (GD) 0 and continuing until 12 months of age. With the exception of splenic CD4-/CD8-cells in female mice only, no alterations were observed in splenic T-cell populations, numbers of splenic B220+ cells, or in lymphocyte proliferation at 12 months of age. Furthermore, populations of all thymic T-cell subpopulations were decreased in male but not female mice following exposure to 14,000 ppb TCE. Autoantibody levels (anti-dsDNA and anti-GA) were assessed periodically from 4 to 12 months of age. Over this period, no increase in autoantibody levels as compared to control was detected, suggesting that TCE did not contribute to or accelerate the development of autoimmune disease markers following lifetime exposure. Not only does this study offer encouraging results, but it is the first study to approach the development of autoimmunity in a novel lifetime exposure paradigm, using an autoimmune prone model, at environmentally relevant exposure levels.

Keywords:

• TCE
• trichloroethylene
• immune
• developmental
• autoimmune
• MRL +/+

Acknowledgments

The authors would like to thank Raymond Kivi and Jennifer Berger-Ritchie for assistance with manuscript preparation. This research was supported by the Medical Research Service, Ralph H. Johnson VAMC and by Contract DE-FC09-02CH11109 from the Department of Energy to the MUSC Environmental Biosciences Program.

Notes

∗Significantly different from respective control (P ≤ 0.05).

^a(organ mass/body mass)∗100.

∗Significantly different from respective control (P ≤ 0.05). DP = CD4+/CD8+. DN = CD4-/CD8-

∗Significantly different from respective control (P ≤ 0.05). DP = CD4+/CD8+. DN = CD4-/CD8-

^AAssuming 30 days/month

^BAssuming drink 4 mL/day

^CAssuming drink 4 mL/day and weight is 25 g (This is a max possible dose as exposure during in utero and lactation periods is assumed to be the same as from weaning to 8 weeks of age and weight is assumed to be 25 g. Although, admittedly, this changes throughout the study).

^Dppm = mg/kg = mg/L = 1000 ppb.

^EAverage adult mouse weight for given strain.

^FAssuming drink 4 mL/day and weight is 40 g (this is a max possible dose as exposure during in utero and lactation periods is assuming to be the same as from weaning to 12 months of age and weight is assumed to be 40 g. Although, admittedly, this changes throughout the study).

^G12 mth = 1 year = 365 days + 21 days gestation = 386 d. Assumption of 4 mL of water/day is based on averages from studies in our lab with TCE and drinking water and the Assistant Laboratory Animal Technician training manual.