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The cytokines NAP-1 (IL-8), MCP-1, IL-1 beta, and GRO in rabbit inflammatory skin lesions produced by the chemical irritant sulfur mustard

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Abstract

Developing and healing dermal inflammatory lesions were produced in rabbits by the topical application of dilute sulfur mustard (SM),9 the military vesicant. In tissue sections of such lesions, cells containing the mRNA of important cytokines were identified with in situ hydridization techniques. These cytokines were neutrophil attractant/activation protein-1 (NAP-1 (also called IL-8)), monocyte chemoattractant (activating) protein 1 (MCP-1), interleukin 1 (beta) (IL-1 (beta)), and GRO (a growth factor and chemokine). Mononuclear cells (mainly macrophages and activated fibroblasts) contained the mRNA of all four of these cytokines. A higher percentage of cytokine-producing mononuclear cells (macrophages and activated fibroblasts) was present in lesions at 2 days (their peak size) than at 6 days, when they were almost healed. Granulocytes emigrated from the bloodstream, passed through the lesions, and were the major constituent of the protective crust. This sequence correlated with the distribution of cells able to produce NAP-1: At 2 days and 6 days, the mononuclears that contained messenger RNA for this granulocyte chemoattractant were found mainly in the upper part of the dermis. At 2 days and 6 days, cells containing the mRNA of IL-1, a primary cytokine, were also found predominantly in the upper dermis, i.e., nearest the site of injury. In contrast, mononuclears containing the mRNA of MCP-1 (a monocyte chemoattractant), and the mRNA of GRO (a granulocyte chemoattractant) were more equally distributed throughout the dermis. SM stimulated hair follicle epithelial cells to up-regulate GRO mRNA and, to a lesser degree, NAP-1 mRNA. Apparently, the irritation produced by SM directly or indirectly induces such epithelial cells to manufacture these growth factors. In the rabbit, hair follicles are known to be the main source of new epithelial cells after the covering epithelium has been destroyed. Therefore, GRO is probably a major autocrine-paracrine stimulus for such repair. A brief review of the role of cytokines in dermal inflammation is presented.

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Abbreviations

SM:

Sulfur mustard: bis(2-chloroethyl)sulfide

GM-CSF:

Granulocyte-Macrophage Colony Stimulating Factor

GRO:

A member of the CXC subfamily of chemokines that promotes the multiplication of cells, formerly called melanoma growth stimulating activity (MGSA)

IFN:

(gamma)-Interferon-gamma

IL-1:

Interleukin 1

IL-8:

Interleukin 8 (same as NAP-1)-a CXC chemokine

MCP-1:

Monocy te Chemoattractant (Activating) Protein-1-a C-C chemokine

NAP-1:

Neutrophil Attractant/Activating Protein-1 (same as IL-8)-a C-X-C chemokine

TGF (beta):

Transforming Growth Factor (beta)

TNF (alpha):

Tumor Necrosis Factor (alpha)

EDTA:

Ethylenediamine tetraacetate

DEPC:

Diethylpyrocarbonate

PBS:

Phosphate-buffered saline solution

PGE2 :

Prostaglandin E2

PGI2 :

Prostaglandin I2 (prostacyclin)

SSC:

Sodium chloride-sodium citrate solution

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Authors and Affiliations

  1. Departments of Environmental Health Sciences, School of Hygiene and Public Health, Baltimore, Maryland

    Junji Tsuruta, Katsunori Sugisaki & Arthur M. Dannenberg Jr

  2. Departments of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Baltimore, Maryland

    Phoebe Mounts

  3. Departments of Epidemiology, School of Hygiene and Public Health, Baltimore, Maryland

    Arthur M. Dannenberg Jr

  4. Department of Pathology, School of Medicine The Johns Hopkins University, Baltimore, Maryland

    Arthur M. Dannenberg Jr

  5. Laboratory of Immunobiology, National Cancer Institute, Frederick, Maryland

    Teizo Yoshimura

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  1. Junji Tsuruta
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  2. Katsunori Sugisaki
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  4. Teizo Yoshimura
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  5. Yasuharu Abe
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On leave of absence from the Institute for Medical Immunology, Kumamoto University School of Medicine, Kumamoto, Japan.

On leave of absence from the Department of Internal Medicine, Oita Medical University, Oita, Japan.

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Tsuruta, J., Sugisaki, K., Dannenberg, A.M. et al. The cytokines NAP-1 (IL-8), MCP-1, IL-1 beta, and GRO in rabbit inflammatory skin lesions produced by the chemical irritant sulfur mustard. Inflammation 20, 293–318 (1996). https://doi.org/10.1007/BF01488205

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