The Role of IL-6 in Irritant Dermatitis

Details

• Personal Author:
  Adelson D ; Gallucci RM ; Ihnat M
• Description:
  Of reported occupational injury associated with workman's compensation, contact dermatitis ranks second most prevalent over all, and irritant contact dermatitis (ICD) is the most common. If specific immune mediators can be associated with irritancy, this will be of significant predictive value when judging the response of an individual to irritant exposure. One such mediator, interleukin 6 (IL-6) is closely associated with skin maintanence. Thus, the hypothesis was proposed that modulation of skin IL-6 levels contributes to severity of dermatitis. Genetic analysis from a database of approximately 600 volunteers exposed to irritants, indeed showed that certain changes in IL-6R and related genes, were associated with ICD severity. Using mouse models, the protective effects of IL-6 are associated with altered barrier and/or inflammatory mediator expression were investigated. Using three genetically altered strains of mice; one that lacks IL-6, one that lacks the receptor for IL-6 in skin, and one that lacks the receptor in inflammatory cells, it was found that irritant dermatitis was worse in all three strains of mice using two chemically distinct irritants. Further, while each mouse strain had a specific inflammatory mediator and cell type signature associated, specific common genes appeared to be associated with severe ICD and may prove to be predictive markers for risk assessment in humans. Since humans vary from one another by multiple gene changes resulting in wholistic immune propensities or "phenotypes", two mouse strains of known immune phenotypes were also assessed for their response to irritants. The C57BL/6 mouse strain is known to show a propensity towards anti-viral immunity, whereas the Balb/c mouse has an anti-parasitic immune preference. ICD was induced in these mice, and inflammation was evaluated. Indeed, it was found that C57 mice had worse ICD as compared to Balb/c and the skin inflammatory mediators and cell types varied greatly between mouse types, again indicating specific inflammatory signatures that can be associated with ICD severity. One mediator in particular, IL-22, was found to be closely associated with skin thickening, a particularly troublesome result of ICD, throughout the mouse models and may serve as both a biomarker for risk assessment as well as a target for therapy. To investigate these inflammatory signatures in much greater depth, skin dermatitis samples from the IL-6 deficient (genetic), as well as the C57BL/6 and Balb/c (phenotypic) mice were analyzed for very broad gene expression using NextGen RNA sequencing (RNAseq). This analysis showed approximately 3 million gene expression changes associated with each immune phenotype and ICD severity, indicating differences as well as commonality in expression that should be of great use in human risk assessment. Further, the skin bacterial populations were also assessed by sequencing, and profound changes were found to be associated with both immune phenotype as well by mere IL-6 deficiency, that may contribute to ICD severity. This shows further that ICD is not just a product of the skin, but its associated microbiome. The knowledge gained from these investigations will provide the basis for future intervention research to reduce the incidence of occupationally related irritant contact dermatitis. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Immune System Irritants Occupational Health Safety Skin
• Keywords:
  Animal Studies Contact Dermatitis Genetic Factors Immune Reaction Skin Exposure
• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• Place as Subject:
  Oklahoma ; OSHA Region 6
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-22
• NIOSHTIC Number:
  nn:20057001
• NTIS Accession Number:
  PB2019-101423
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-010241, 2018 Nov; :1-22
• Contact Point Address:
  Randle M. Gallucci, Ph.D. (PI), Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma, Health Sciences Center, 1110 N. Stonewall, Oklahoma City, OK 73117-1200
• Email:
  Randy-gallucci@ouhsc.edu
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing ; Oil and Gas Extraction
• Performing Organization:
  University of Oklahoma Health Sciences Center, Oklahoma City
• Peer Reviewed:
  False
• Start Date:
  20130901
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c4994d9bbb3f6453deaafbd447a53d8427dd17d084d6446d77d2b7ff6a2d1d91f02d423e3cf3304fd759d4b1825b78be6edbc4dc9511454c0f5b1268d73c5bb9
• Download URL:
  https://stacks.cdc.gov/view/cdc/218921/cdc_218921_DS1.pdf
• File Type:
  [PDF - 5.79 MB ]