Topical cyclosporine: effects on allergic contact dermatitis in guinea pigs

Cyclosporine (CSA) is an effective immunosuppressive agent and is used in tissue transplantation. The present investigation was undertaken to determine the effect of topical delivery of CSA on allergic contact dermatitis in guinea pigs. Topical 15% CSA in an azone (1-dodecylazacycloheptan-2-one)-containing vehicle blocked local elicitation in previously dinitrochlorobenzene (DNCB) sensitized animals that received a single topical application just prior to elicitation. Elicitation was not blocked at a distant site, indicating a local effect of topical CSA. In contrast, topical CSA when applied twice daily for a total of 5 applications during sensitization only, did not block subsequent elicitation. These experiments suggest that cyclosporine may be beneficial in the therapy of human contact dermatitis, as well as other T cell mediated dermatoses.     

A new animal model for contact dermatitis: the hairless guinea pig.

Allergic and irritant contact reactions were evaluated in the recently identified hairless guinea pig, Crl:IAF(HA)BR, a mutant from the Hartley strain. The cutaneous changes were observed macro- and microscopically. The irritant contact dermatitis was induced by croton oil, 2,4-dinitrochlorobenzene (DNCB), or anthralin. Both hairless and hairy guinea pigs developed similar reactions to these chemicals. The density of the epidermal Langerhans cells (LC) of hairless guinea pigs was significantly higher than that in the hairy strain. Allergic contact sensitization was easily induced with DNCB. Photoallergic contact sensitization was also induced with tetrachlorosalicylanilide (TCSA) but not with tribromosalicylanilide (TBS). However, by administration of cyclophosphamide before sensitization, positive photocontact responses were seen with TBS. These results indicate that hairless guinea pigs can be used as animal models for investigation of immunologic and nonimmunologic contact reactions.     

Nickel-sulphate-induced contact dermatitis in the guinea pig maximization test: a dose-response study

Nickel sulphate is a sensitizer in guinea pigs, but the frequency of sensitization varies from study to study. The dose-response relationship for NiSO4.6H2O was evaluated in the guinea pig maximization test in this study. 6 intradermal (0.01%-3.0% aq.) and 6 topical (0.25%-10.0% pet.) concentrations were chosen for induction and NiSO4.6H2O 1% pet. was used for challenge, based on the absence of skin irritation in a pilot study. Blind reading was performed. A logistic dose-response model was applied to the challenge results. At 48 h, a linear relationship was obtained between the intradermal induction dose (but not topical dose) and the response, resulting in a maximum sensitization rate of 40% after 3% i.d. The reactivity disappeared at re-challenge 1 week later. Following a booster closed patch on day 35, using NiSO4 10% pet., the animals were challenged with NiSO4 2% pet. and statistical analyses of 72-h readings revealed a non-linear dose-response relationship, giving a maximum response frequency of 40% after initial induction with NiSO4 3% i.d. and 2% topical.     

Influence of area of application of allergen on sensitization in contact dermatitis

There are at least 2 quantitative variables when applying allergens to obtain sensitization: the absolute amount of allergen and the surface concentration. This review analyzes the limited studies on surface concentration and determines surface area threshold levels for the allergens documented in the literature.     

UVB serum factor: suppression of allergic contact dermatitis in guinea pigs

Serum from guinea pigs exposed to a single high dose of UVB and from controls was injected into the spleen of normal animals 5 days prior to sensitization. When 1.0 ml was transferred 4.5 h after irradiation, immunosuppression was obtained. Transfer of 1.5 ml of serum 2.5 h after irradiation failed to induce immunosuppression. This experimental model in guinea pigs might be valuable in further studies investigating the effect of other modalities of ultraviolet exposure (e.g., PUVA or high-dose UVA) on the release of soluble serum factor(s) inducing immunosuppression in allergic contact dermatitis.     

Comparison of methods for the macroscopic assessment of epicutaneous allergic contact reactions in guinea pigs

40 guinea pigs were sensitised with a 50% solution of 2,4-dinitro-1-chlorobenzene (DNCB) and challenged 14 days later with DNCB 0.05%. Four parameters were determined to evaluate the challenge reaction after 24, 48, 72 and 96 h: (a) intensity of erythema, (b) reaction area (product of the largest diameters of the reaction in vertical alignment), (c) increase in skinfold thickness and (d) reaction volume (product of the reaction area and the increase in skinfold thickness). The test reactions were read blind by 2 independent observers, yielding small but significant differences in all methods except determination of the reaction area. Further statistical analysis revealed a linear correlation between the intensity of erythema and the other 3 parameters determined, as well as between the reaction area and the reaction volume. In contrast, the increase in skinfold thickness did not correlate linearly either with the reaction area or the reaction volume. When the results of the 24- and 48-h readings were compared, the characteristic crescendo reaction of contact allergy was demonstrable by all methods except the determination of the reaction area. After the 48-h reading, a continuous decrease of reactions was found with all methods. It is concluded that the determination of the reaction area and consequently of the reaction volume are not suitable for exact measurement of epicutaneous allergic contact reactions in guinea pigs. The most precise results will be obtained by measuring the increase in skinfold thickness, whereas the determination of the intensity of erythema, which is easier to perform, may be sufficient for many purposes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced skin threshold to irritation in the presence of allergic contact dermatitis in the guinea pig

The skin is more susceptible to irritation when an active eczematous process is present. This reduced threshold to irritation occurs in skin distant from the site of the eczematous skin. Data is presented to demonstrate the appearance of irritant dermatitis to lower concentrations of sodium lauryl sulfate during the presence of an allergic contact dermatitis in the guinea pig.     

Structure-activity relationships in allergic contact dermatitis induced by methacrylates

Some methacrylates are known to be strong contact sensitizers. To determine the effect of side-chain length on sensitizing potential, we examined 11 derivatives with linear side chains from C₁ to C₁₈ in an experimental sensitization test in guinea pigs. The results showed an increase in the sensitizing potential with increasing length of the alkyl side chain from Q to C₁₂. The C₁₂ derivative, lauryl methacrylate, showed the strongest sensitizing potential. Further elongation of the alkyl side chain of methacrylates resulted in a decrease in the potential. With respect to the side-chain-length-dependent sensitizing potential, the present results correspond well with the findings obtained with other compounds like primin, catechols, phenols, hydroquinones, and gallates.     

Effect of a new topical cyclosporin formulation on human allergic contact dermatitis

We studied the effect of a new topical cyclosporin (CS) formulation on the suppression of allergic contact dermatitis. 4 test sites were outlined on the back of healthy male volunteers. For 7 consecutive days, the test sites were treated as follows: #1: CS formulation (10%), #2: placebo formulation, #3: flumethasone pivalate (FP) formulation (0.02%; #4: no treatment. On day 8, we challenged all test sites in the diphenylcyclopropenone (DCP) sensitized individuals. Photographic and clinical documentation was performed daily. 24 h after the DCP skin challenge, a marked redness accompanied by severe itching and slight pain occurred in the test sites pretreated with CS (#1) and placebo (#2). A considerably milder reaction was noted in the untreated test site (#4) and only a faint redness was noted in the test site pretreated with FP (#3). After 36 h, a further increase in the cutaneous reaction was documented in CS and placebo pretreated test sites (#1, 2). In agreement with other workers, topical CS did not suppress experimentally-induced allergic contact dermatitis in man. On the contrary, in CS and placebo pretreated areas (#1, 2), an increased cutaneous reaction was observed. This observation may be explained by the extensive pretreatment with the topical formulation of CS and placebo, which possibly caused a profound perturbation of the stratum corneum, enabling excessive allergen penetration compared to the untreated area with intact stratum corneum.     

Clonidine: irritant and allergic contact dermatitis assays

Clonidine in petrolatum, clonidine transdermal device, and its placebo device were assayed for relative irritancy potential (21-day cumulative irritancy assay) and allergic contact dermatitis potential (Draize repeat insult patch test assay). Both clonidine in petrolatum and the clonidine transdermal device appear to be of minimal irritancy potential. Only the clonidine device demonstrated, in the Draize assay (and in clinical trials), allergic contact dermatitis potential. Its relatively delayed onset of demonstration of allergic contact sensitization in clinical trials requires investigation as to mechanism.     

A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test

This paper presents precise sensitization test data of 15 chemicals with a wide spectrum of sensitization potencies, and proposes a new protocol and criteria for quantitative evaluation of sensitization potencies of chemicals. The tests were performed according to the design of Magnus-son and Kligman, changing the application concentrations for induction as well as for challenge phases. 3-dimensional relationships between mean response (or sensitization rate), induction and challenge concentrations were found in all chemicals tested. The following 2 values are proposed as a quantitative measure of sensitization potency: (a) the minimum induction concentration that induces a positive response; (b) the challenge concentration that induces a mean response approximately equal to 1.0 among the animals applied with the highest concentration for induction. Both values coincided with each other within the range of 1 order of magnitude in every compound except 2. The values varied by 5 orders or more of magnitude among the compounds, showing a wide variation of sensitization potencies among chemicals. A good correlation was found for every chemical between the value of sensitization potency thus obtained and the residual levels in causative products in human cases of allergic contact dermatitis. A new experimental protocol for obtaining values (a) and (b) is proposed.     

Putative skin-protective formulations in preventing and/or inhibiting experimentally-produced irritant and allergic contact dermatitis

The effectiveness of skin protective formulations was evaluated in a previously-described in vivo human model. All formulations failed to inhibit ammonium hydroxide and urea irritation. Only paraffin wax in cetyl alcohol statistically (p<0.01) reduced Rhus allergic contact dermatitis. 3 commercial formulations markedly (p<0.001) suppressed sodium lauryl sulfate irritation. Paraffin wax in cetyl alcohol was quantitatively the most effective formulation. These results suggest that some formulations may provide protective effects against certain, but not all, irritants or allergens.     

Cutting oil dermatitis on guinea pig skin

We assessed the effect of repeated application of cutting oil on 9 guinea pigs' skin by visual scoring and skin water vapour loss measurement. The visual scores (severity score) were significantly higher on skin treated with cutting oil (positive control) compared to untreated skin (negative control). The corresponding mean SVL values were also significantly higher. We also assessed the effect of 2 barrier creams on the 9 guinea pigs' skin treated with cutting oil. The visual scores on skin treated with either barrier cream were significantly higher than positive control skin. The corresponding mean SVL values on skin treated with either barrier cream were also higher (not statistically significant). It appeared that the 2 barrier creams did not confer protection against the irritant effect of the cutting oil. On the contrary, barrier creams appeared to exacerbate the irritant effect of cutting oil.     

Predictive evaluation in animals of the contact allergenic potential of medically important substances I. Comparison of different methods of inducing and measuring cutaneous sensitization

Groups of guinea pigs were sensitized with a 0.1% solution of dinitrochlorobenzene (DNCB) by the Draize intracutaneous method, The course of the induction process, the influence of the vehicles used and the extent to which the reactions are amenable to assessment according to objective criteria were examined. The sensitivity of the standardized Draize test was then compared with that of various other sensitization techniques, including:
The intracutaneous test with adjuvant (optimization test)
The maximization test according to Magnusson & Kligman (1969)
The epidermal sensitization test
The epidermal sensitization lest wish prior irritation of the contact site (by croton oil or sodium lauryl sulphate).
Comparison of these methods revealed that either the additional application of adjuvant or prior irritation of the contact site augmented the degree of sensitization to DNCR just as greatly as the simultaneous use of adjuvant and prior irritation of the skin, (maximization test.). The improved sensitization methods, and in particular the standardised optimization test, may prove to be of particular value for the study of so-called weak allergens.     

Cutting oil dermatitis on guinea pig skin

The effect of repeated exposure of cutting oil on 8 guinea pigs' skin was evaluated by visual scoring for erythema and skin water vapour loss (SVL) measurement over a 6-week period. The visual scores (measuring severity of erythema) and SVL values were significantly higher on skin treated with cutting oils (positive control) compared to untreated skin (negative control) throughout the study period. The scores and SVL values returned to near-baseline values when cutting oil application was stopped. In addition, the effect of 2 "after-work" emollient creams on 8 guinea pigs' skin repeatedly treated with a cutting oil was assessed by similar methods. The visual scores and SVL values of guinea pig skin that was repeatedly treated with the cutting oil and moisturized with "after-work" emollient creams, were significantly higher than negative and positive control guinea pig skin. It appeared that the 2 "after-work" emollient creams do not alleviate the irritant effect of the cutting oil on guinea pig skin. They appeared to aggravate the irritant effect of the cutting oil.     

外用茶油对变应性接触性皮炎发生的影响

目的 观察茶油对小鼠变应性接触性皮炎发生的影响。方法 建立二硝基氟苯致小鼠变应性接触性皮炎模型,外用药物进行治疗,观察发生皮炎的小鼠耳片的组织学变化（HE染色）,RT-PCR检测组织中炎症细胞因子IL-2、IFN-γ mRNA的表达水平。结果 成功建立二硝基氟苯致小鼠变应性接触性皮炎的动物模型,且皮肤中IL-2、IFN-γ mRNA的表达显著增高。哈西奈德溶液组和茶油组的耳片组织肿胀明显减轻,炎症反应轻微,炎性细胞浸润数目少,组织病理变化轻。在茶油和哈西奈德溶液的干预下,炎性组织IL-2、IFN-γ的mRNA表达均不同程度下降。结论 茶油减轻二硝基氟苯致小鼠变应性接触性皮炎的病理损害,下调了炎症因子的表达。