ISSN:
1365-2222
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background Down-regulation or modulation of T cell activity by immunosuppressive drugs is an effective treatment in diseases where exaggerated T cell responses play a role. A primary effect of the anti-inflammatory drugs (AIDs) is inhibition of the synthesis of growth factors, such as IL-2, thereby down-regulating T cell proliferation. However, it is still largely unknown to what extent these AIDs are able to down-regulate specifically type-1 or type-2 T cell cytokine production, and whether they can down-modulate chemokine receptor expression, thereby preventing migration of T cells to the site of inflammation.Objective We investigated the suppressive effect of dermatologically used AID (cyclosporin A (CsA), lactoferrin (LF), 1α, 25-dihydroxyvitamin D3 (VD3), hydrocortisone (HC), di-methyl-fumarate (DMF), diclofenac (DF)) on both type-1 and type-2 T cells. Since allergic contact dermatitis is a skin disorder in which an exaggerated T cell response of both types of T cell subsets can be observed, we used this disorder as a model to study the capacity of AID to suppress type-1 or type-2 T cell responses.Methods Peripheral blood mononuclear cells of nickel allergic patients were cultured in the presence of allergen and increasing concentrations of AID. Proliferation was determined by measuring 3H thymidine incorporation; chemokine receptor (CCR10, CCR4, CXCR3) expression was studied by flow cytometric analysis and IFN-γ or IL-5 cytokine production was measured by ELISA.Results Three major patterns can be distinguished regarding the effect of AID on T cell responses. The first group, including CsA and LF, inhibited non-selectively T cell proliferation, chemokine receptor expression and cytokine production, with CsA as the most potent drug tested. A second group of AID, which included VD3, HC and DMF, suppressed mainly type-1 T cell responses, as revealed by strong interference with IFN-γ production and CXCR3 expression, and limited effects on either or both IL-5 and CCR4 expression. The third pattern was displayed by DF, which down-regulated IL-5 production and CCR4 expression, whereas IFN-γ and CXCR3 were unaltered.Conclusions Using a contact allergy model, we have demonstrated that various AIDs show distinct pharmacological profiles in that either type-1 or type-2 or both T cell responses are suppressed. These results should contribute to a more rational selection of AID in treating inflammatory skin diseases mediated by either or both of these T cell subsets.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-2222.2004.02124.x
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