Differential Skin Inflammatory Responses in Irritant Contact Dermatitis

Details

• Personal Author:
  Calhoun KN ; Gallucci RM ; Luckett-Chastain LR
• Description:
  Irritant contact dermatitis (ICD) is characterized as an inflammatory response caused by topical exposure to irritants and is regulated by cytokines. However, intrapersonal and interpersonal variability is observed with ICD, thus suggesting that the pathophysiology is more complex than originally thought. Differential cytokine profiles and dermal cellular phenotypes are thought to be responsible for this variability, and are modulated by the nature of the irritant. Immune phenotype, such as Th1- and Th2-dominance, and interleukin 6 (IL-6) deficiency are also postulated to contribute to this variability. To determine how these factors modulate the pathomechanism of ICD, C57BL/6 ("Th1 dominant"), Balb/c ("Th2 dominant"), and IL-6 deficient (IL-6KO) mice were exposed to the occupational irritants, benzalkonium chloride (BKC) and JP-8 jet fuel for 3 days to induce ICD. Lesions were obtained for histological examination, assessment of cytokine expression, and identification of dermal cells. Histopathology revealed that BKC induces greater cellular infiltration than JP-8, especially in C57 and IL-6KO mice. However, Balb/c mice did exhibit epidermal hyperplasia after JP-8 exposure. Following BKC exposure, C57 showed up-regulation of IL-1B, IL-18, TNF-y, CCL3, CCL4 and CXCL2 compared to Balb/c mice and higher expression of IL-27, CCL3, CCL5, CCL11, and CXCL2 compared to IL-6KO. After JP-8 exposure, C57 exhibited decreased expression of IL-28, IL-18, CCL2, and CCL5 compared to Balb/c mice and reduced expression of IL-10 compared to IL-6KO. C57 mice exposed to BKC had greater infiltration of neutrophils and granulocytes compared to Balb/c, but following JP-8 exposure Balb/c mice had more granulocyte infiltration. IL-6KO mice responded to irritant exposure by increased infiltration of dendritic cells compared to C57 mice. Overall, C57 mice develop a more severe form of ICD in response to BKC in comparison to Balb/c; however, Balb/c mice manifest a quicker inflammatory response to JP-8 exposure. In both Th1- and Th2- dominant phenotypes, the pathomechanism of ICD induced by BKC involved activated neutrophils, whereas JP-8 induced ICD did not. IL-6 deficiency appears to cause greater dendritic cell infiltration into the dermis in response to BKC and JP-8. The aforementioned findings may provide a better understanding of the pathology of ICD and insight into specific targets for therapeutic immunomodulation. [Description provided by NIOSH]
• Subjects:
  Animals Immune System Irritants Occupational Health Safety Skin
• Keywords:
  Animal Studies Contact Dermatitis Cytokines Immune Reaction Skin Exposure
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; Oklahoma ; OSHA Region 3 ; OSHA Region 6
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20057003
• Citation:
  Toxicologist 2017 Mar; 156(1):460
• Federal Fiscal Year:
  2017
• 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:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1e201d7b804e2aa8d3214b1dc3bf5fdcddd3526f7dbf5617eebdd912dfd3d043bae2811a2778ac29b2fd01663291e79a4ed735f1e94e0ce6c0f7dd4c63e98807
• Download URL:
  https://stacks.cdc.gov/view/cdc/214486/cdc_214486_DS1.pdf
• File Type:
  [PDF - 897.91 KB ]