Role of Firefighting-Associated Chronic Stress Factors in Immune Dysfunction in Mouse Model

Details

• Personal Author:
  Yadav B ; Yadav JS
• Description:
  Background: Firefighters, like many other occupational groups, perform long work shifts involving nightshift and thus remain sleep deprived. Increasing evidences suggest that sleep deprivation (SD) induces stress or injury, in multiple organs and thus may predispose individuals to development of different diseases. Indeed, SD has been associated with many disease like type 2 diabetes mellitus, obesity, cancers, cardiovascular disease, infections, among others. Firefighters undergo stress due to sleep deprivation and exposure to hazardous chemicals such as in the firefighting foams (e.g perfluorooctanoic acid/PFOA). Independent human studies have shown that SD leads to alteration in immune function in multiple ways, such as inducing IFN-y secretion, decreasing phagocytosis in peripheral blood cells, decreasing lymphocyte proliferation, decreasing NK cell count and target cell killing activity and decreasing antibody production from plasma B cell PFOA is widely used in fire extinguishing foams and a number of industrial and consumer products and has been frequently detected in food-chain and drinking water and bioaccumulates in kidneys, liver and blood. Animal studies have suggested that PFOA has immune suppressive effects and causes different type of cancer in rodents. In mice, PFOA causes decreased T cell-dependent antibody production. Serum PFOA levels were negatively associated with response to diphtheria and tetanus vaccination in children. Hypothesis: Collectively, these facts coupled with the reports of sleep deprivation associated stresses in high risk jobs lead us to hypothesize that occupational SD-induced chronic stress modulates immune homeostasis and function, which may be further exacerbated by co-exposure to perfluorooctanoic acid (PFOA). This alteration in immune parameters, may at least in part, can serve as a tool for finding novel biomarkers and help understand the mechanism of different disease conditions as a result of firefighting- related exposures. Objectives Aim 1: To assess sleep deprivation (SD)-associated chronic stress in an SD mouse model based on biomarkers. Aim 1a: We will use the established multiple platform method to induce sleep deprivation and chronic stress mice model. Aim 1b: To analyze sleep deprivation induced chronic stress associated bio-markers (cortisol and C-reactive protein) by ELISA in serum. Aim 2: To examine the effects of co-exposure (SD + PFOA) on stress and immune function in the SD mouse model. Aim 2a. Immune cell phenotyping and immune mediator profile will be measured based on qRT-PCR analysis. (Gene- T-bet, Fox-p3, IL-10, TNF-a, IL-1β, IL-6, IFN-y, Cxcl5, NK1.1, Cxcl11) Study plan: A mouse model of sleep deprivation based on the reported modified multiple platform method will be set up by using 6-8 week old C57BL/6 mice (n=8 mice/ group). Briefly, in this method, the mice will be placed in a water cage (e.g. 42 cm×28 cm×18 cm high), containing six platforms (3 cm in diameter), surrounded by water up to 1 cm beneath the platform surface for 24 h. Ad libitum food and sterile water will be given to mice during the sleep deprivation period. Chronic stress will be induced by following the sleep deprivation scheme outlined in Figure-1 without or with weekly co-exposure to PFOA (@ 1ug/kg mice body weight, which is equivalent to the range of reported PFOA level in firefighters) by oral gavaging on day 7, 14 and 21. Limitations: We anticipate no specific technical problems in inducing SD and performing PFOA exposure given our prior experience in mouse studies in mentor's laboratory. We expect no obvious problems in sampling and immunological analysis considering the PI's specialization in immunology and mentor laboratory's track record in environmental immunology and established routine lab techniques. However, it is possible that some mice may die due to SD induced stress in the middle of the experiment. In that case, we will continuously monitor the mice and shorten the duration of the SD cycle to a level enough to induce measurable stress indicators. Expected results: 1. We expect to identify alterations in immune cells profile in mice with the SD-induced stress without and with PFOA exposure, in a differential manner. This information is expected to provide insights into the interplay between the SD induced stress and PFOA exposure 2. we expect to identify novel specific immune biomarker candidates associated with SD-induced stress and/or PFOA exposure Future directions: 1. This study will unravel the risks as result of chronic stress due to occupational risk factors sleep deprivation and PFOA exposure. 2. This work will reveal specific deployable biomarkers in different body fluids as a result of altered immune status. 3. Preliminary data obtained through this pilot study will be used to submit a larger grant to NIOSH to pursue future expanded studies on role of firefighting-associated chronic stress factors in immune dysfunction of occupational workers and associated health disorders and diseases in firefighters. [Description provided by NIOSH]
• Subjects:
  Animals Firefighters Fires Immune System Occupational Exposure Occupational Health Safety Sleep Sleep Initiation And Maintenance Disorders
• Keywords:
  Animal Studies Chronic Exposure Fire Extinguishing Agents Fire Fighters Fire Fighting Immune Reaction Immune System Disorders Long Work Hours Sleep Deprivation Stress
• Publisher:
  University of Cincinnati
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1
• NIOSHTIC Number:
  nn:20058652
• Citation:
  20th Annual Pilot Research Project Symposium, University of Cincinnati Education and Research Center, October 10-11, 2019, Cincinnati, Ohio. Cincinnati, OH: University of Cincinnati, 2019 Oct; :1
• CAS Registry Number:
  Perfluorooctanoic acid (CAS RN 335-67-1)
• Federal Fiscal Year:
  2020
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  20th Annual Pilot Research Project Symposium, University of Cincinnati Education and Research Center, October 10-11, 2019, Cincinnati, Ohio
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6f20ef134e5524255d8eb7849d60cc1f8e2c650c4e1add71b7a529b01621b6c7bd26382f835dfcebd1893bd695e23ee66ce631be865128fcb8a459f2a287fdba
• Download URL:
  https://stacks.cdc.gov/view/cdc/221693/cdc_221693_DS1.pdf
• File Type:
  [PDF - 280.15 KB ]