Dissertation
Dissertation > Medicine, health > Dermatology and Venereology > Dermatology > Allergic and toxic skin diseases > Dermatitis ( drug eruption )

Study on Immunological Effect Biomarkers and Allergen of Dermatitis Medicamentosa-like of Trichloroethylene

Author ZuoDan
Tutor DaiYuFei
School Disease Control and Prevention Center
Course Health Toxicology
Keywords Trichloroethylene Trichloroacetic acid Trichloroethanol delayed hypersensitive reaction biomarker
CLC R758.25
Type Master's thesis
Year 2011
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The prevalence of Dermatitis medicamentosa-like of trichloroethylene (DMLT) in workers shows a rising trend year by year, which appears to be a serious occupational health issue. Little is known about its pathogenesis to date, currently, the view that ODMLT is similar to delayed hypersensitive reaction according to its clinical characteristics was accepted widely. TH1 (helper T cell 1)/TH2 (helper T cell 2) immune balance system acts as an important aspect in the mechanism of immune regulation system. Cytokines and inflammatory factors such as nitric oxide (NO) play an important role in Th1/Th2 immune balance system. Disorder of cytokines or NO level can result in the imbalance of immune regulation system, and trigger a series of abnormal immune responses, which maybe an important aspect in the pathogenesis of DMLT. At present, there is still no final conclusion about the special hapten of DMLT.The purpose of the present study has been twofold:(1) to investigate the possible immunological effect biomarkers of DMLT; (2) to confirm the special hapten of DMLT, and assess the allergenic potential of trichloroacetic acid (TCA) and trichloroethanol (TCOH). The main results as follows:一The exploration of immunological effect biomarkers of DMLTSerum samples of 22 patients of DMLT,22 healthy TCE-tolerant individuals and 22 healthy non-TCE-exposed individuals were determined the production of cytokines such as IL-1β(interleukin-1β), IFN-γ(interferon-γ), TNF-α(tumor necrosis factor-α), IL-5(interleukin-5), IL-10(interleukin-10), MCP-1(macrophage chemoattractant protein-1), MIP-1β(macrophage inflammatory protein-1β), IL-8(interleukin-8) and NO.The results as follows:(1)The difference among three groups:The production of IL-1β,IFN-γ, IL-5, IL-10, IL-8, MCP-1,MIP-1βin patients of DMLT were significant higher than other two groups(P<0.05), The production of TNF-αin patients of DMLT only was significant higher than TCE-tolerant controls(P<0.05), and no significant difference was found in the patients of DMLT and healthy non-TCE-exposed (P>0.05); No significant difference was found in the level of NO in three groups (P=0.065). (3) The relation between 8 cytokines with NO, lymphocyte and eosnophils amounts in 21 patients of DMLT in the early of disease. The results as follows:there were significant positive correlation between almost 8 cytokines (P<0.05); the high production of IL-5 was significant related with the increased amounts of eosnophils (P=0.016). but no significant correlations between 8 cytokines with the amounts of lymphocyte were found; NO showed different degree of correlation with 8 cytokines, especially, and there was a significant positive correlation between NO and IL-8, MIP-1β,IL-1β(P<0.05).We could infer that:Th1/Th2 immune imbalance system acts as an important aspect in the process of DMLT. Particularly, The abnormal production of IL-1β, TNF-α, IFN-γ, IL-8, MCP-1, MIP-1 (3, IL-5, IL-10 all played important roles in the process of DMLT. These cytokines can be used as referential indexes for the early health surveillance, the clinic disease treatment and prognosis assessment.二The assessment of allergen of DMLT.1 The Assessment of the allergenic potential of TCA and TCOH through THP-1 cell line invitro testTHP-1 cells (5 X 105/ml)were treated respectively with different concentration of TCA(final concentration of 0.5,1.0,2.0,4.0mmol/L), TCOH(final concentration of 0.5,1.0,2.0,4.0 mmol/L)and 2,4-dinitrochlorobenzene(final concentration of 0.0010,0.0025,0.0050 mmol/L), following 48h of incubation, the release of IL-8 was evaluated by sandwich ELISA,IL-8 production was increased following the increasing of stimulation concentration in any chemical treatment group. In contrast to control cells, IL-8 production was significantly increased after stimulation with 0.005mmol/L2,4-dinitrochlorobenzene,1.0,2.0,4.0 mmol/L TCOH; 1.0,2.0,4.0 mmol/L TCA(P<0.05). However, induced nitric oxide synthase (iNOS) production didn’t show a consistent increasing trend following the increasing of stimulation concentration of chemical tested. In contrast to control cells, iNOS production was increased after stimulation with 0.0025mmol/L2,4-dinitrochlorobenzene,2.0,4.0 mmol/L TCOH,4.0mmol/LTCA.In this study, we could infer that TCA maybe a contact allergen and have an important relation with DMLT. And more study to confirm the relation of TCOH with DMLT. 2 Test for function of antigen-specific lymphocyte proliferation in humanWe choosed 4 groups subjects:10 patients of DMLT,20 TCE-exposure healthy workers,20 non TCE-exposed workers and 7 patients of DMLT(healed patients of 10 patients), and incubated the peripheral blood lymphocytes (1×106/ml)in different concentrations of chemicals (0.5mmol/TCA,2.0mmol/L TCA,0.5mmol/L TCOH,2.0mmol/L TCOH) for 48 hours, lymphocytes from healed patients group challenged with the high and low concentrations of TCA showed significantly higher cell proliferation than other three groups subjects. However, no significant difference was found between random two groups of other three groups. No significant difference also was found in the lymphocytes cell proliferation among the four groups challenged with either concentration of TCOH. The conclusion was:TCA maybe a special hapten of DMLT, and more studys needs to investigate the effect of TCOH in DMLT.In conclusion, the aim of this study includes two parts:one is to investigate the function of cytokine and nitric oxide in DMLT; another is to assess the allergenic potential of TCA and TCOH. The results as follows:on the one hand, Th1/Th2 immune balance system plays an important role in the process of DMLT. Particularly, the abnormal production of IL-1β, TNF-α, IFN-y, IL-8, MCP-1, MIP-1β, IL-5, and IL-10 were closely related with DMLT. These cytokines can be used as referential indexes for the early health surveillance, the clinic disease treatment and prognosis assessment; on the other hand, TCA maybe a special hapten of DMLT. And TCOH was only preliminary screened as a potential contact allergen in THP-1 cell in vitro test, More studies should be planted to investigate the function of TCOH in the pathogenesis of DMLT.

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