Immune dysfunction in the skin in atopic dermatitis and its modulation by Chinese herbal therapy

Atopic dermatitis (AD) is a chronic, eczematous condition with an associated aberration of the immune system, specifically in the regulation of immunoglobulin E (IgE) production. This study was designed to investigate the effects of Chinese herbal therapy (CHT) on atopic dermatitis, both in patients and in an animal model of cell mediated immunity in the skin. Further, through dissection of the phenotypic status of immunocompetent cells within the skin biopsies obtained from patients and animals, it was aimed to determine whether CHT induced clinical improvement was associated with changes in the disposition of these immunocompetent cells. By using in-situ hybridisation to detect the possible relationship of cytokine mRNA levels with the changes of cell subsets and the clinical improvement, an attempt to gain knowledge of the immune reaction involved was also made. The results showed a significant improvement in the clinical status of AD patients after two months treatment with CHT, as determined by the skin condition measured by scores of erythema and surface damage. Immunohistochemical studies demonstrated significant reduction in T cell numbers expressing HLA-DR and macrophages expressing low affinity receptors for IgE (CD23+) in the lesional skin from AD patients after efficacious CHT treatment. In-situ hybridisation revealed that certain cytokine mRNA levels in the lesional skin in AD patients were altered by CHT therapy. Specifically TGFp mRNA levels exhibited a reverse correlation with the scores of erythema in AD patients. In placebo controlled experiments performed in guinea pigs, CHT showed a consistent effect in reducing skin reactivity when sensitized animals were challenged with dinitro-chlorobenzene (DNCB). Immunohistochemical studies on guinea pig skin biopsies showed that the improved skin condition was associated with reduced T cell reactivity as seen in AD patients. This study confirms previous reports that treatment with CHT significantly reduces eczema activity as measured by erythema and surface damage scores. It goes further in identifying quantifiable reductions in immunological parameters in the dermis of treated subjects, specifically significant reductions in the number of macrophages expressing FceRII receptors (low affinity receptors for IgE) and in T cells expressing HLA-DR. Although a higher number of cells expressing FceRI (High affinity receptors for IgE) were identified in the lesional skin in AD patients, the fact that efficacious CHT therapy did not altered the number of cells expressing FceRI adds further weight to the hypothesis that FceRII expression contributes to the inflammatory process in this disease. FceRI, on the other hand, may be of less pathological significance than the expression of FceRII. The study also shows evidence of a CHT induced shift of CD23 expression from antigen presentation cells to phagocytes within the macrophage populations of the skin biopsies of AD patients. Finally, the placebo controlled animal model revealed effects of CHT on moderating the recall reaction to DNCB in the skin while showing no effect on the induction of immune reactivity. This further confirms that within the herbs of the CHT, are efficacious factors that can modulate the immune dysfunction associated with atopic eczema. An immunohistochemical study of guinea pig biopsies revealed a similar pattern of changes in immunological parameters to those found in AD patients, and suggested that the guinea pig model could be suitable to test isolated components of CHT as efficacious treatment of atopic dermatitis.