Study On Index Of Cell-mediated Immunity And Pathogenesis Of Dermatitis Medicamentosa-like Of Trichloroethylene

Dermatitis medicamentosa-like of trichloroethylene(DMLT) in workers appears to be an occupational health issue and has aroused general concern in China in recent years. However, little is known about its pathogenesis to date, there are also lack of specific indexes for health surveillance as well as specific measures for clinical treatment.DMLT may involve in typeⅣhypersensitivity according to its characteristics. Formation of T memory lymphocytes and proliferation are the two steps of cell-mediated immunity. Activated T cells regulate the proliferation of NK and B cells through secrete a series of cytokines. Cytotoxic T lymphocytes(CTL) play an important part in cell-mediated immune system. Its cytotoxicity can be induced by two ways:a) granule-dependent exocytosis pathway, which participate immune defenses. b) Fas-FasL intercellular linkage-mediated pathway, which down-regulate immune response through clean activated peripheral CTL at the end of the immune response. The two ways play an important role in maintaining the immune homeostasis. The process of DMLT may related to the proliferation of lymphocytes and the function of CTL. Those two approaches play an important role in cleaning foreign antigens to maintain immune homeostasis. In normal condition, specific immune lymphocytes which stimulated by antigen proliferate in peripheral immune organs. In the end of the immune response, the activated cells apoptosis through Fas/FasL pathway, thus to control the immune process and maintain immune homeostasis. Therefore, DMLT might be induced by activated cells which were not cleared in time, and strong immune response breakout.In order to test the above hypothesis, we conducted a three groups design analysis and cases analysis to explore the relationship between abnormal index of cell-mediated immunity and DMLT. The results were as follows:1. Study on Index of Cell-mediated immunity and Pathogenesis of DMLTThere are there groups in this study:case group, cases are 16 patients of DMLT, all examinations executed on admission; TCE-exposure group,32 workers came form the workshops the cases occurred but no skin disorders examined by the occupational physicians after the first 3 months of TCE exposure. Healthy worker group,28 workers were never exposed to TCE and no history of previous skin disease. The main results are as follows:Ⅰ.Test for functions of antigen-specific lymphocyte proliferationPeripheral blood lymphocytes(2×106/ml) of three groups cultured with different concentrations TCE (0.2mmol/L,1mmol/L,5mmol/L). In any group, peripheral blood lymphocyte relative survival rates gradually reduced with the increase of TCE concentration. No significant difference was found about relative survival rates of lymphocytes under the same concentrations in three groups. The result suggest that TCE performed great cell toxicity on peripheral blood lymphocytes, and there was no TCE-specific memory lymphocyte.Ⅱ. Analysis of lymphocyte subsets in peripheral blood16 patients with severe rash, accompanied by different degree of liver damage, 15 cases (93.33%) in 16 with higher ALT and 12 cases (73.33%)in 16 with higher AST. From the routine blood test of 16 patients,14 cases(87.6%) neutrophils (NEUT) higher than normal clinical range; 8 cases(50%) eosinophils(EO) higher than normal clinical range. In both healthy TCE-exposed workers and unexposed workers, the indexes are all in clinical normal reference ranges. The change of peripheral immune cells are closely related to the organization of immune cell infiltrates, NEUT increase can make liver damage, the results are consistent with the liver founction detection. Human EO mainly distributed in the respiratory tract, enteron and genitourinary tract mucosa tissue, the increase of EO in peripheral blood might relate to the damage of mucous membrane in eye, mouth and genital of patients.The absolute counts of lymphocyte, T cell, CD4+T cell were significantly increased in patients with hypersensitivity dermatitis compared with healthy TCE-exposed workers and unexposed workers(P<0.05); meanwhile, no significant differences in counts of lymphocyte, T cell, CD4+T cell were demonstrated between exposed and unexposed groups(P>0.05), so those three indexes could be disease markers of DMLT. CD8+T cell, CD8+CD28- T cell counts among the three groups showed case group>exposed group>unexposed control group, and the difference was significant(P<0.05). NK cell counts among the 3 groups showed the case group0.05). The expression of FasL in CD8+T and CD4+T cell in case and exposed group are higher than unexposed group(P>0.05). It indicate that there are active T cell in both cases and healthy TCE exposure wokers, CTL (CD4+CTL and CD8+CTL) induce apoptosis of effector cells in healthy TCE-exposed workers timely. However, in cases, some CTLs are removed through Fas/FasL pathway, others might migrate to skin, liver, kidney, etc, and mediated the target cell apoptosis. Meanwhile, the high expression of PF and GrB cause skin damage in cases. 2.8 cases report of DMLTCompare the differences of DMLT when hospitalized and liver function recovered to normal, further explore the indexes of immunological changes and that could be used to evaluate the clinical treatment effect, and combining with the former group analysis to analyze the relationship between immunological indexes and DMLT.Comparing to when liver function recovered to normal, NEUT, EO increased and CD4+/CD8+ratio decreased when hospitalized, those indexs returned to normal with the improvment, and could reflect the recovery of disease. CD4+T cells were lower before treament than rehabilitation, it did not consistent with the former research, and indicate the increase of CD4+T cells relecant to treatment. CD4+T cells could not be used as early immunological screening index of the disease.Fas and FasL in CD8+T cells, PF and GrB protein in peripheral lymphocyte were higher when hospitalized than liver function recovered to normal, Those results are consistent with the former results. Those all indicate CTL may be involved in the multiple organ damage of DMLT.In summary, this study revealed the immune response in DMLT might induced by the metabolites of TCE rather than TCE itself. There were great changes in DMLT about lymphocyte subsets in peripheral blood. Lymphocyte and T cell could be disease markers of DMLT, CD8+T, CD8+CD28- T and NK cell could be effect makers for TCE exposure. CTLs take part in the damage of skin,liver,kidney and some other organs. Those results could make some significance to health surveillance of TCE exposure and provide possibility for further studies in pathogenesis.