Registros de Litología

Despite the clinical improvement and immunohistological changes in lesional

skin after treatment of CHT, there was no significant changes in any cell subsets in

non-lesional skin after treatment (p > 0.05 in all cases)(Fig 3.3.8).

7-1 6- ë 4- %

I

% 2-1 1- ■ i Before CHT ^ After CHT

. J â

C D 2 3 1 5 A 5 2 2 E 7 R F D l C D l R F D 7 C D 4 5 R o C D 2 5 T m ix

Fig 3.3.8 Mean ( ±SD) number of cells expressing specific phenotypic markers in non-lesional biopsies taken before and after treatment with CHT. Data is from 8 subjects. Statistical analysis reported in text.

3.4

Comments

This study has identified quantifiable reductions in immunological

parameters in the dermis following treatment with CHT. Specifically, significant

reductions in the number of dendritic cells expressing FcsRII receptors and in those

expressing HLA-DR were seen. As well as a reduction in the numbers of cells

showing positivity for these phenotypes, the level of expression of these antigens

was also found reduced in lesional skin. The observed association between CD23

expression and clinical severity was taken as cogent evidence to support an

hypothesis proposed earlier that aberrant expression of CD23 may contribute to

pathogenesis (Takigawa et al. 1991).

It is important to stress that this was not a placebo controlled study. It

remains a possibility therefore that the reductions in immunological parameters

reported represent natural variation in the disease process. However non-lesional

skin (exhibiting increases over previously reported values from normal control skin)

did not alter following treatment. This and the magnitude and consistency of

reduction in inflammatory parameters following treatment make it unlikely that this

variability was purely a reflection of the natural progression of the disease, but

more likely a result of efficacious therapy. Nevertheless a definite study will require

a placebo controlled trial or a placebo controlled experiment on animal models.

It is now accepted that atopic eczema is associated with activated T-

1989). This fact is further substantiated by the success of treatment with cyclosporin

(Hanifin and Rajka, 1980; Salek et al. 1993), which vigorously reduces the number

of activated T-cells in the lesions and the expression of the IL-2 receptor (Hanifin

and Rajka, 1980).

A link between atopic activity involving IgE antibody responses to allergens

and the promotion of T-cell activation has been found in studies of facilitated

antigen presentation (van der Heijden et al. 1995). In vitro investigations revealed

that IgE allergen complexes may be endocytosed by antigen presenting cells and

allergens subsequently presented to T-lymphocytes. This mechanism is dependent

on IgE receptors on antigen presenting cells (Maurer and Stingl, 1995). Following

initial observations of IgE bound to the surface of dendritic cells in the dermis of

patients with atopic dermatitis, several groups have now demonstrated the presence

of high affinity (Bieber et al. 1992; Wang et al. 1992; Grabbe et al. 1993) and low

affinity (Buckley et al. 1993; Poulter et al. 1991) receptors for IgE on these cells. It

has been shown that lesional skin in atopic dermatitis represents a delayed

hypersensitivity reaction (Buckley et al. 1995) in this context the unchanged

C D 4+ /C D 8+ subset ratio after treatment indicates that no preferential cell

emigration or selection process was influenced during the treatment.

Although clinical benefits of CHT were associated with reductions in cell

numbers and the expression of phenotype markers (including the receptors for IgE)

in lesional skin; there was, no significant change in these cell populations in non-

studies that there were abnormalities of the cell populations in clinical normal (non-

lesional) skin when compared with skin from normal subjects (Li et al. 1992). The

reason why CHT did not affect these cell populations in non-lesional skin is not

clear.

In the present study efficacious therapy is associated with reductions in

expression of the low affinity receptors for IgE while no change was seen in the

numbers of cells expressing high affinity receptors. Despite the fact that high

affinity receptors for IgE are expressed on more cells in lesional skin than that in

non-lesional skin (see results 3.3.3), there was no significant change in the number

of cells expressing high affinity receptors for IgE after CHT. In contrast, a

significant reduction in the number of CD23+ cells was observed in lesional skin

after CHT.

The fact that CHT fails to alter the number of cells expressing the high

affinity receptor does not discount the possible significance of this mechanism.

Expression of high affinity IgE receptors by Langerhans cells is seen as a

constitutive event (Wang et al. 1992) but expression of FcsRII on dermal dendritic

cells only emerges in pathologic situations (Buckley et al. 1992a). Indeed a switch

of CD23 positivity from tissue macrophages to dendritic cells has been found to

represent the major difference between the immunopathology of contact dermatitis

and atopic dermatitis (Buckley et al. 1992b). Furthermore the fact that regulation of

patients (Renz et al. 1992) adds further weight to the hypothesis that FceRII

expression contributes to the inflammatory process in this disease. The reported role

of FcsRI expression in promoting T cell activation (van der Heijden et al. 1995;

Maurer and Stingl, 1995) may thus be of less pathological significant than

expression of FceRII. Although definite evidence for the involvement of the latter in

facilitated antigen presentation has not as yet been reported, this possibility must

exist and may possibly have a more dramatic effect on pathogenesis.

As the regulation of inflammatory reactions is achieved in part by the

cytokine network, any change in the relevant balance of the network may alter the

progress of the disease. Thus investigation of the possible involvement of cytokines

In document Desarrollo de un simulador para análisis e interpretación de registros eléctricos de pozos petroleros (página 51-56)