interleukin-8 and Dermatitis--Occupational

Cytokines play an important role in skin inflammation.. We determined whether polymorphisms in cytokine genes contribute to the occurrence of occupational chronic irritant contact dermatitis (CICD).. In a case-control study, 9 polymorphisms in the genes coding for interleukin (IL)-1 alpha, IL-1 beta, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha were determined in 197 patients with CICD. 217 apprentices in vocational training for high-risk occupations for CICD served as controls.. For all polymorphisms, no differences in genotype distributions were found between patients and controls. However, in patients with self-reported low levels of wet work and irritant exposure, more TNFA -308 variant genotypes (G/A and A/A) were present compared with those exposed to higher levels or controls, which indicates a TNFA-induced increase of susceptibility. In patients with TNFA -308 variant genotypes, the prevalence of flexural eczema was higher (48% and 57%) compared with that in patients presented with wild-type genotype (30%). Regarding IL1A -889, prevalence of symptoms of dermatitis was lower in apprentices with T/T or C/T genotype (32% and 36%) compared with wild-type genotype (54%, C/C). This indicates a protective effect of these variant alleles in acquiring hand dermatitis.. This study provides evidence that some genetic variations alter susceptibility to (chronic) dermatitis. Knowledge of the impact of genetic differences on the risk of CICD is essential in predictive testing of individuals at risk.

Topics: Adolescent; Adult; Case-Control Studies; Chronic Disease; Dermatitis, Atopic; Dermatitis, Irritant; Dermatitis, Occupational; DNA; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Hand Dermatoses; Humans; Interleukin-10; Interleukin-1alpha; Interleukin-1beta; Interleukin-8; Logistic Models; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha

Cutting fluids are widely used in the metal-machining industry to lubricate and reduce heat generation when metals are cut by a metal-cutting tool. These cutting fluids have caused occupational irritant contact dermatitis (OICD), and many of the additives used in these cutting fluid mixtures are thought to be responsible for OICD in workers. The purpose of this study was to assess single or various combinations of these additives in initiating the OICD response following an acute 8-hour exposure in porcine skin in vivo and in vitro using the isolated perfused porcine skin flap (IPPSF) and human epidermal keratinocytes (HEK). Pigs (n = 4) were exposed to 5% mineral oil (MO) or 5% polyethylene glycol (PEG) aqueous mixtures containing various combinations of 2% triazine (TRI), 5% triethanolamine (TEA), 5% linear alkylbenzene sulfonate (LAS), or 5% sulfurized ricinoleic acid (SRA). Erythema and edema were evaluated and skin biopsies for histopathology were obtained at 4 and 8 hours. IPPSFs (n = 4) were exposed to control MO or PEG mixtures and complete MO or PEG mixtures, and perfusate samples were collected hourly to determine interleukin- (IL-) 8 release. The only significant (p < 0.05) mixture effects observed in IPPSFs were with SRA + MO that caused an increase in IL-8 release after 1 or 2 hours' exposure. In vivo exposure to TRI alone appeared to increase erythema, edema, and dermal inflammation compared to the other additives, while SRA alone was least likely to initiate a dermal inflammatory response. In 2-component mixture exposures, the presence of TRI appeared to increase the dermal inflammatory response at 4 and 8 hours especially with the PEG mixtures. In the 3- and 4-component mixtures, MO mixtures are more likely to incite an inflammatory response than PEG mixtures. TRI exhibited the highest toxicity toward HEK, which correlates well to the in vivo irritation and morphology results. In summary, these preliminary studies suggest that the biocide, TRI, is the more potent of the 4 performance additives in causing dermal irritation, and this may vary depending on whether the worker is exposed to a synthetic (PEG)- or MO-based fluid. These findings will however require further clinical studies to validate these acute dermal effects as well as human cumulative irritation following exposure to similar cutting fluid formulations in the workplace.

Topics: Animals; Cell Survival; Cells, Cultured; Dermatitis, Contact; Dermatitis, Occupational; Dose-Response Relationship, Drug; Female; Humans; Interleukin-8; Kidney; Metallurgy; Mineral Oil; Occupational Exposure; Skin; Skin Absorption; Swine

The identification of potential damage due to chemical exposure in the workplace is a major health and regulatory concern. Traditional tests that measure both sensitization and elicitation responses require the use of animals. An alternative to this widespread use of experimental animals could have a crucial impact on risk assessment, especially for the preliminary screening of new molecules. We developed an in vitro model for the screening of potential toxic compounds. Human keratinocytes (HaCat) were used as target cells while matrix metalloproteinases (MMP) were selected as responders because they are key enzymes involved in extracellular matrix (ECM) degradation in physiological and pathological conditions. Chemical exposure was performed using nickel sulphate as a positive tester. Nickel contact induced upregulation of MMP-2 and IL-8 mRNA production. Molecular activation occurred even at very low nickel concentrations even though no phenotypic changes were observed. MMP-9 accumulation was found in the medium of treated cells with respect to controls. These observations led to the hypothesis that even minimal exposure can accumulate transcriptional activity resulting in long-term clinical signs after contact. Our simple in vitro model can be applied as a useful preliminary complement to the animal studies to screen the effects of new potential toxic compounds.

Topics: Animal Testing Alternatives; Biomarkers; Cell Line; Cell Survival; Dermatitis, Contact; Dermatitis, Occupational; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-8; Keratinocytes; Matrix Metalloproteinases; Models, Biological; Nickel; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Toxicity Tests; Up-Regulation

Epoxy resin compounds (ERC) include a large number of chemicals, such as epoxy resins (ER), reactive diluents and hardeners. Many hardeners, e.g., aliphatic polyamines, are well-known sensitizers. Another type of ER hardeners are the phthalic anhydrides, such as methylhexahydrophthalic anhydride (MHHPA) and methyltetrahydrophthalic anhydride (MTHPA), which have been reported as causing immunologically-mediated respiratory diseases and contact urticaria, but not allergic contact dermatitis. Here, we present a horizontal boring-machine worker who developed allergic contact dermatitis, as well as allergic rhinitis and an immediate contact skin reaction from MHHPA. Patch testing with a dilution series of MHHPA in pet. elicited the following results: 2%, 1% and 0.5%, +2; 0.25% and 0.125%, + (3- to 6-day readings). An immunohistochemical and electron microscopic study also indicated that the patch test reactions were conventional-delayed allergic reactions. Interleukin 8 was observed in the epidermal cells, whereas interleukin 4 immunoreactivity was detected in the dermal cells. Immunoreactivity to-interleukin 5, granulocyte/macrophage-colophony stimulating factor (GM-CSF) or eosinophil cationic protein was not seen. In conclusion, the patient developed both Type I and Type IV allergy to MHHPA. The clinical data, patch test results, immunohistochemical and electron microscopic observations indicated that the MHHPA allergy detected by the patch test reaction was a conventional delayed-type hypersensitivity reaction. The patient also had an allergic patch test reaction to para-phenylenediamine and diaminodiphenylmethane, possibly representing occupational sensitization.

Topics: Allergens; Aniline Compounds; Blood Proteins; Dermatitis, Allergic Contact; Dermatitis, Occupational; Eosinophil Granule Proteins; Eosinophils; Epidermis; Epoxy Resins; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immunohistochemistry; Inflammation Mediators; Interleukin-4; Interleukin-5; Interleukin-8; Male; Microscopy, Electron; Middle Aged; Patch Tests; Phenylenediamines; Phthalic Anhydrides; Respiratory Hypersensitivity; Rhinitis; Ribonucleases; Skin; Urticaria