Biology Ph.D. Dissertations

Title

Deciphering the Link Between Polychlorinated Biphenyls, Immune Function and Exercise

Date of Award

2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Biological Sciences

First Advisor

Lee Meserve (Advisor)

Second Advisor

Howard Cromwell (Other)

Third Advisor

Todd Keylock (Committee Member)

Fourth Advisor

Scott Rogers (Committee Member)

Fifth Advisor

Vipaporn Phuntumart (Committee Member)

Abstract

Polychlorinated biphenyls (PCBs) are environmental pollutants and endocrine disruptors, harmfully affecting reproductive, endocrine, neurological and immunological systems. This has implications for processes such as wound healing, which is modulated by the immunological response of the body. Conversely, while PCBs can be linked to diminished wound healing, outside of PCB pollution systems, exercise has been shown to accelerate wound healing. However, the potential for moderate intensity exercise to modulate or offset the harmful effects of a toxin like PCB are yet unknown. Exploration of this possible moderation on local immune response was achieved by measuring wound size and analyzing the concentrations of proinflammatory cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), keratinocyte chemoattractant (KC), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-a (TNF-a) in wounds (inflicted by punch biopsy) in mice that were not exercised as compared with those previously exercised at moderate intensity by running on a treadmill for 30min/day and then injected intraperitoneally with Aroclor 1254 (industrial mixture of PCB congeners) in doses of either 0, 100, 500 and 1000 ppm (wt/wt of mice). Mice were euthanized at Day 3 or Day 5 (n = 3-6) and skin excised from the wound area was homogenized and analyzed for cytokine content. Systemic effects of exercise on immune function in PCB exposed animals were examined by lipopolysaccharide (LPS) challenge (intraperitoneal injections) and analyzed by measuring the average body temperatures using a thermal imaging camera. Wound healing data revealed that in animals not exercised only the greatest dose of PCB (1000 µg/g) showed a pattern for faster wound healing. Exercise produced a pattern of more rapid wound healing rates compared to the animals administerd similar doses, except for animals administered 100 µg/g PCB. Concentrations of pro-inflammatory cytokines revealed patterns that could explain many of the changes observed in the wound healing rates and could be used as a good predictor of progression of wound healing. Average body temperature measurements revealed a febrinergic response to LPS stimulation only in the mice not exercised that were not administered PCB. In exercised mice this response was blunted, indicating lowered inflammatory response. Overall, exercise appears to have a beneficial effect on wound healing and LPS stimulation, only in animals not administered PCB. Recent studies show both PCB and exercise impair functioning of macrophages and that could have produced the similarity of results in the present study and needs to be further explored.

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