Effects of environmentally-relevant levels of perfluorooctane sulfonate on clinical parameters and immunological functions in B₆C₃F₁ mice

Abstract

In the first part of a series of studies to account for perfluorooctane sulfonate (PFOS)-induced sheep red blood cell (SRBC)-specific immunoglobulin M (IgM) antibody suppression in mice, a survey of clinical and immunotoxicological endpoints was examined. Adult female B₆C₃F₁ mice were exposed orally for 28 days to a total administered dose (TAD) of 0, 0.1, 0.5, 1, or 5 mg PFOS/kg. Uterus wet weight was significantly decreased compared with control at the 5 mg/kg dose. No indications of wasting syndrome, malnutrition, alteration of thyroid homeostasis, or signs of overt toxicity were observed. Numbers of splenic CD19⁺/CD21⁻, CD19⁺/CD21⁺, B220⁺/CD40⁺, CD4⁺/CD154⁻, CD4⁺/CD154⁺, and MHC-II⁺ cells were not altered. Additionally, ex vivo interleukin-4 (IL-4), IL-5, and IL-6 production by in vitro anti-CD3- or phorbol myristate acetate-stimulated CD4⁺ T-cells was not affected. Ex vivo IL-6 production by B-cells was significantly increased by in vitro stimulation with either anti-CD40 or lipopolysaccharide. Increased IL-6 production by B-cells was the most sensitive endpoint assessed resulting in alterations at the lowest dose tested (0.1 mg/kg TAD) following anti-CD40 stimulation. Further studies are required to characterize effects on inflammatory markers such as IL-6 at environmentally relevant concentrations of PFOS and to determine the key events associated with PFOS-induced IgM suppression to address potential human health risks.

Keywords::

• Perfluorooctane sulfonate
• PFOS
• immune
• cytokines
• toxicity
• CBC
• hematology

Acknowledgements

The authors would like to thank the following reviewers for their critical review of the manuscript: Drs. Malcolm Meaburn and Mike Twiner and Mr. Jeff Adams. We acknowledge the Medical University of South Carolina (MUSC) and the Hollings Cancer Center for their support of the Flow Cytometry & Cell Sorting Shared Resource Facility. This publication does not constitute an endorsement of any commercial product or intend to be an opinion beyond scientific or other results obtained by the National Oceanic and Atmospheric Administration (NOAA). No reference shall be made to NOAA, or this publication furnished by NOAA, to any advertising or sales promotion that would indicate or imply that NOAA recommends or endorses any proprietary product mentioned herein, or which has as its purpose an interest to cause the advertised product to be used or purchased because of this publication. The authors have no conflict of interest to declare.

Declaration of interest

The authors report no declaration of interest. The project was funded in part by a grant from National Institutes of Environmental Health Sciences 1R03ES014058-01A1 (MMPA) and the National Oceanic and Atmospheric Administration/National Ocean Service/Center for Coastal Environmental Health and Biomolecular Research.