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Biomedical subjects

B Homey

Publications and source records attributed to B Homey.

46 records · Page 3Linked to original sources
PubMed1998

A modified murine local lymph node assay for the differentiation of contact photoallergy from phototoxicity by analysis of cytokine expression in skin-draining lymph node cells.

Since predictive differentiation of photoallergenic from phototoxic reactions, induced by low molecular weight compounds, represents a current problem, we tried to improve the differentiation between the two reactions by using a modified protocol of the local lymph node assay (LLNA). Briefly, groups of female BALB/c mice received compound solution or vehicle alone on the dorsum of both ears on 3 consecutive days. Immediately after compound application indicated groups of mice were exposed to a UVA light-dose of 10 J/cm2. Auricular lymph nodes draining the ear tissue were excised 24 h following the last exposure. Evaluation consisted of assessing lymph node weights and cell counts to monitor organ hyperplasia and in vivo-proliferative events following substance application. Furthermore, we analysed cytokine gene transcription in freshly prepared lymph node cells (LNC) and the cytokine release in vitro by restimulated CD4+ T-cells and antigen presenting cells (APC), both purified from the skin-draining lymph nodes. Both contact (photo) allergenic (oxazolone and tetrachlorosalicylanilide) and phototoxic substances (8-methoxypsoralen and acridine) caused a dose dependent increase in lymph node weights and cell counts pointing to an inflammatory process in the lymph nodes. Analysis of cytokine gene transcription ex vivo and cytokine release in vitro revealed that during the induction phase of contact (photo) allergy CD4+ T-cells produced IL-2 and IFN-gamma as well as IL-4 and IL-10, whereas IL-6 was derived from APC. In contrast, phototoxic reactions caused only an upregulation of IL-2 and IFN-gamma. Furthermore, we demonstrate that the release of IL-4 and IL-10 by CD4+ T-cells was clearly increased, whereas IL-6 and IFN-gamma expression was reduced or not changed following a challenge with contact (photo) allergens revealing an allergy-indicative shift in cytokine expression. In conclusion, our results show that contact photoallergenic reactions could be differentiated from phototoxic events by analysis of LNC cytokine expression patterns.

Animals↗
PubMed1998

An integrated model for the differentiation of chemical-induced allergic and irritant skin reactions.

Contact and photocontact allergic as well as irritant and photoirritant skin reactions represent a major problem in clinical dermatology and during the development of new pharmaceuticals. Furthermore, there is a lack of in vitro and in vivo assays that provide a clear differentiation between allergic and irritant skin reactions. Here, we describe an integrated model to differentiate between chemical-induced allergic and irritant skin reactions by measuring objective and easy-to-determine parameters within both skin and skin-draining lymph nodes. Dose-response studies with standard contact and photocontact allergens as well as irritants and photoirritants revealed that irritants predominantly induced skin inflammation, which in turn stimulated draining lymph node cell proliferation. In contrast, the induction phase of contact or photocontact allergy was characterized by marginal skin inflammation, but a marked activation and proliferation of skin-draining lymph node cells. Therefore, a differentiation index (DI) was defined describing the relation between skin-draining lymph node cell activation (lymph node cell count index) and skin inflammation (ear swelling). A DI > 1 indicates an allergic reaction pattern whereas DI < 1 demonstrates an irritant potential of a chemical. Experiments with the contact allergen oxazolone, the photocontact allergen TCSA + UVA, the irritant croton oil, and the photoirritant 8-methoxypsoralen + UVA confirmed the predictive value of DI. Furthermore, flow cytometric analysis of lymph node-derived T- and B-cell subpopulations revealed that contact sensitizer, but not irritant, induced the expression of CD69 on the surface of I-A+ cells. In conclusion, further studies with a broad range of irritants and allergens will be required to confirm general applicability.

Animals↗
PubMed1998

Preferential relative porphyrin enrichment in solar keratoses upon topical application of delta-aminolevulinic acid methylester.

Topically applied delta-aminolevulinic acid is used efficiently for the treatment of solar keratoses by photodynamic therapy. Recent animal studies suggest that porphyrin sensitization of epithelial tissue is improved by using esters rather than free delta-aminolevulinic acid. The present study examines porphyrin metabolite formation after topical application of delta-aminolevulinic acid or delta-amino-levulinic acid methylester in human solar keratoses versus adjacent normal skin. Level of total porphyrins, porphyrin metabolites and protein were measured in skin samples excised after 1 and 6 h. Higher levels of porphyrins were observed in solar keratoses than in normal skin with both substances. Maximum porphyrin levels were present in solar keratoses treated with delta-aminolevulinic acid for 6 h. However, the ratio of porphyrins in solar keratoses versus adjacent normal skin was higher with delta-aminolevulinic acid methylester. The pattern of porphyrins showed no significant difference between normal and afflicted skin, protoporphyrin being predominant. The results suggest that application of free delta-aminolevulinic acid may be more effective in sensitizing solar keratoses. However, treatment with delta-aminolevulinic acid methylester leads to a preferential enrichment of porphyrins within lesional skin.

Administration, Topical↗
PubMed1997

A local lymph node assay to analyse immunosuppressive effects of topically applied drugs.

Topical glucocorticosteroids represent the mainstay of antiinflammatory therapy in the treatment of inflammatory skin diseases. Their clinical use, however, is limited by local and systemic side-effects. Thus, in dermatopharmacology there is a large demand for alternative non-steroidal antiinflammatories. Other than transplantation models, most of the frequently used in vivo test systems for assessment of drug-induced immunosuppression measure changes in inflammatory skin responses by means of skin erythema and edema after challenge of sensitized animals. The aim of this study was to develop an alternative mouse model to detect and analyse immunosuppressive effects of topically applied drugs. On the basis of a modified local lymph node assay, we analysed effects of topical hydrocortisone, dexamethasone, mometasone furoate and FK506 (tacrolimus) during the induction phase of contact hypersensitivity. On 4 consecutive days, NMRI mice were treated on the dorsal surfaces of both ears with increasing concentrations of test compound. During the last 3 days, the mice received in addition the contact sensitizer, oxazolone (1%). On day 5, draining auricular lymph nodes were removed in order to assess lymph node cell counts and perform flow cytometric analysis of lymph node cell subpopulations (CD4+/CD25+, Ia+/CD69+, Ia+/B220+). All test compounds proved to exert significant immunosuppressive effects after topical application, but showed differences in their immunomodulatory potential. In conclusion, the local lymph node assay serves as an appropriate model to characterize immunosuppressive effects of topically applied drugs by measuring immunologically relevant end-points.

Administration, Topical↗
PubMed1996

FK506 in the treatment of inflammatory skin disease: promises and perspectives.

The immunosuppressive macrolide drug FK506 is currently gaining increasing importance in dermatopharmacology. Here, Gunter Michel and colleagues summarize the current state of research into the molecular mechanisms responsible for the functional modulation of cell types other than T cells, particularly epidermal cells, by this drug.

Animals↗
PubMed1996

Effect of topical cis-urocanic acid on local lymph node activation during contact sensitization in mouse, rat and guinea-pig.

Cis-urocanic acid (cUCA) has been suggested as a mediator of impairment of contact hypersensitivity induction by ultraviolet B (UVB) irradiation. We ascertained whether topical cUCA influences local lymph node activation during induction of contact hypersensitivity. Topical cUCA or vehicle was applied during the local lymph node assay to oxazolone. Local lymph node weight and cell number were assessed in all animals. Additionally, cell proliferation rate was studied in Hartley guinea-pigs and CBA/Ca mice, whereas activation of antigen-presenting cells was quantified in NMRI mice and Wistar rats. Topical cUCA suppressed all parameters of local lymph node activation due to oxazolone application in guinea-pigs. No effect, with the exception of a suppression of antigen-presenting cell activity, was seen in mice. No effect was seen in rats. The study shows that topical cUCA may suppress local lymph node activation during contact sensitization and suggests that differences between the effect of cUCA in different animal species may exist.

Animals↗
PubMed1994

Topical FK506: suppression of allergic and irritant contact dermatitis in the guinea pig.

Topical FK506 has recently been shown to have an anti-inflammatory effect in vivo in humans. In this study its effects in contact dermatitis were studied in the guinea pig model. Topical FK506 suppressed both irritant and allergic patch-test reactions. The most prominent suppressive effect was seen when skin sites were pretreated with FK506. Topical FK506 did not impair the induction of contact allergy as assessed by challenges, although it suppressed local lymph node cell accumulation during contact allergy induction. Topical FK506 may hold promise as a treatment for skin disorders that respond to oral FK506 or cyclosporin A.

Administration, Topical↗
PubMed1994

Detection of photoreactivity demonstrated in a modified local lymph node assay in mice.

Photoallergic and phototoxic reactions are an increasing problem in dermatologic practice. Currently available test models are heterogeneous and do not allow differentiation between photoallergic and phototoxic reactions. We have modified the local lymph node assay to screen for photoreactive compounds. We found an ultraviolet A (UVA) irradiation-dependent increase in the weights and cell counts of the auricular lymph nodes after application of 8-methoxypsoralen, tribromosalicylanilide, trichlorosalicylanilide, chlorpromazine and promethazine. In contrast to these photoreactive compounds, contact sensitizers did not produce any reaction to UVA irradiation in the local lymph node assay. This assay system has the advantage of being less expensive and less time-consuming and might even be able to differentiate between phototoxic, photoallergic and contact allergic reactions.

Allergens↗