Goat-anti-canine IgE polyclonal antibody로 유발한 개 피부염에 대한 0.1% FK-506 연고의 항염효과를 평가하였다. 임상적으로 건강한 성견 5두를 사용하여 실험군은 대조군, 위약적용군, FK-506 적용군으로 구분하였다. 항염효과는 팽진의 크기, 피부생검 검사를 통한 비만세포와 호산구수를 측정하여 평가하였으며 비만세포는 Toluidine blue, 호산구는 Luna 염색법을 사용하였다. 염증유발 15분 후의 팽진의 크기는 FK-506 적용군에서 유의성 있게 감소하였다 (p < 0.01). 6, 12, 24 시간 후 염증유발부위에 대한 피부생검을 각각 실시하였다. 정상피부의 비만세포는 $12.32{\pm}3.27cells/mm^2$ 이었으며 12시간 후에 FK-506 적용군은 $5.79{\pm}0.86cells/mm^2$으로 대조군의 $1.89{\pm}0.49cells/mm^2$, 위약군의 $1.74{\pm}0.50$ 에 비해 유의하게 증가하였다(p < 0.01). 정상피부의 호산구는 $2.73{\pm}2.24cells/mm^2$ 이었다. 대조군, 위약 적용군, FK-506 적용군의 호산구 수는 12 및 24 시간 후 FK-506 적용군에서 대조군과 위약 적용군에 비해 유의하게 증가하였다(p < 0.01). 따라서 FK-506 연고는 급성염증과 아토피증상과 유사한 후기염증에서 항염효과 있는 것으로 사료된다.
Goat-anti-canine IgE polyclonal antibody로 유발한 개 피부염에 대한 0.1% FK-506 연고의 항염효과를 평가하였다. 임상적으로 건강한 성견 5두를 사용하여 실험군은 대조군, 위약적용군, FK-506 적용군으로 구분하였다. 항염효과는 팽진의 크기, 피부생검 검사를 통한 비만세포와 호산구수를 측정하여 평가하였으며 비만세포는 Toluidine blue, 호산구는 Luna 염색법을 사용하였다. 염증유발 15분 후의 팽진의 크기는 FK-506 적용군에서 유의성 있게 감소하였다 (p < 0.01). 6, 12, 24 시간 후 염증유발부위에 대한 피부생검을 각각 실시하였다. 정상피부의 비만세포는 $12.32{\pm}3.27cells/mm^2$ 이었으며 12시간 후에 FK-506 적용군은 $5.79{\pm}0.86cells/mm^2$으로 대조군의 $1.89{\pm}0.49cells/mm^2$, 위약군의 $1.74{\pm}0.50$ 에 비해 유의하게 증가하였다(p < 0.01). 정상피부의 호산구는 $2.73{\pm}2.24cells/mm^2$ 이었다. 대조군, 위약 적용군, FK-506 적용군의 호산구 수는 12 및 24 시간 후 FK-506 적용군에서 대조군과 위약 적용군에 비해 유의하게 증가하였다(p < 0.01). 따라서 FK-506 연고는 급성염증과 아토피증상과 유사한 후기염증에서 항염효과 있는 것으로 사료된다.
Five dogs were used to determine whether 0.1% tacrolimus ointment application for one day would inhibit IgE-mediated late-phase reactions (LPRs). It was consisted of three periods: one period without therapeutic administration (control) and two periods of treatment with either the tacrolimus ointmen...
Five dogs were used to determine whether 0.1% tacrolimus ointment application for one day would inhibit IgE-mediated late-phase reactions (LPRs). It was consisted of three periods: one period without therapeutic administration (control) and two periods of treatment with either the tacrolimus ointment or vehicle. Induction of IgE-mediated LPRs was induced by intradermal injections of 0.05 ml (0.14 mg/ml) of solution of goat anti-canine IgE polyclonal antibodies. Each section for mast cells (MCs) and eosinophils (EPs) was stained with acidified toluidine blue, and Luna's stain, respectively. Assessment of anti-inflammatory effect of tacrolimus ointment composed of cell counts of MC and EP from lesions of induced LPR. In normal canine biopsies, the number of dermal MCs and EPs were $12.3{\pm}1.4cells/mm^2$ and $3.1{\pm}1.3cells/mm^2$, respectively. MC counts dramatically decreased at time dependent manner after anti-IgE administration. However, the number of MCs on 6 hours after challenge was significantly less decreased in the groups treated with the tacrolimus, as compared with control and vehicle group. The number of EPs on 24 hours after challenge was significantly lower in the group treated with the tacrolimus than in the control and vehicle groups. In conclusion, this study revealed that 0.1% tacrolimus ointment in dogs may exert a potent anti-inflammatory effect on inhibition of MC degranulation and also secondary prevention of EP infiltration during LPR.
Five dogs were used to determine whether 0.1% tacrolimus ointment application for one day would inhibit IgE-mediated late-phase reactions (LPRs). It was consisted of three periods: one period without therapeutic administration (control) and two periods of treatment with either the tacrolimus ointment or vehicle. Induction of IgE-mediated LPRs was induced by intradermal injections of 0.05 ml (0.14 mg/ml) of solution of goat anti-canine IgE polyclonal antibodies. Each section for mast cells (MCs) and eosinophils (EPs) was stained with acidified toluidine blue, and Luna's stain, respectively. Assessment of anti-inflammatory effect of tacrolimus ointment composed of cell counts of MC and EP from lesions of induced LPR. In normal canine biopsies, the number of dermal MCs and EPs were $12.3{\pm}1.4cells/mm^2$ and $3.1{\pm}1.3cells/mm^2$, respectively. MC counts dramatically decreased at time dependent manner after anti-IgE administration. However, the number of MCs on 6 hours after challenge was significantly less decreased in the groups treated with the tacrolimus, as compared with control and vehicle group. The number of EPs on 24 hours after challenge was significantly lower in the group treated with the tacrolimus than in the control and vehicle groups. In conclusion, this study revealed that 0.1% tacrolimus ointment in dogs may exert a potent anti-inflammatory effect on inhibition of MC degranulation and also secondary prevention of EP infiltration during LPR.
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문제 정의
1% tacrolimus ointment could prevent degranulation of MCs and infiltration of EPs in LPR in normal canine skin. This is the first study investigating the anti-inflammatory effects on one day administration of tacrolimus in the LPR-induced by anti-IgE antibodies.
가설 설정
These patterns strongly indicate the different degranulation or infiltration time kinetics between MC and EP. We hypothesized that many MC degranulation can lead to many EP infiltration during LPR and eventually lead to the exacerbate magnitude of chronic AD lesion. In fact, percutaneous absorption of tacrolimus ointment in canine had higher blood levels at 6 hour post application and this patterns strongly appeared repeated application (21).
제안 방법
Active(0.1% Protopic® Fugisawa, Japan) or placebo ointment were given on days 7 to 8, and days 20 to 21 during 24 hours (Fig 1).
The right side of the thorax was used for the first application and the left side of the thorax for the second application. The active product or vehicle was applied twice a day on day 7, and 20 and once a day the next following day on 8, and 21 before collection specimens.
The principle finding in this study was that the application of the 0.1% tacrolimus ointment for one day inhibited infiltration of MCs and EPs provoked by post injection of antiIgE into canine skin. Collectively, 0.
MCs are crucial role in immediate phase and acute phase of AD lesions; EPs play a pivotal role in late-phase and chronic phase of AD lesions. Therefore, the present study was designed to determine whether a 0.1% tacrolimus ointment could prevent degranulation of MCs and infiltration of EPs in LPR in normal canine skin. This is the first study investigating the anti-inflammatory effects on one day administration of tacrolimus in the LPR-induced by anti-IgE antibodies.
Two of them were female and three were male. This study was performed as a randomized, crossover, and placebo-controlled for the purpose of rule out the active ingredient. It was divided into three periods (Table 1): one period without therapeutic administration (control), and two similar periods of treatment with either the active or vehicle of one day, separated by a wash-out period of 12 days (30).
대상 데이터
Five dogs (3-5 year old) were used in this study. Two of them were Maltese, two were Shih tzu, and the rest was Pekingese.
데이터처리
The counts of MCs and EPs in three groups were compared by student t-test or Mann-Whitney U/Wilcoxon test using computer software (SAS Institute Inc., Cary, NC, USA.). Differences were judged as significant if the p value was ≤ 0.
성능/효과
1% tacrolimus ointment has direct or indirect and rapid anti-inflammatory effects on MCs, and EPs by inhibition on T cell activation, the release of pro-inflammatory mediators and cytokines. These results suggested that tacrolimus can be an effective remedy for AD in point of blocking MC degranulation and reducing EP infiltration, proliferation, and activity.
This study showed that 0.1% tacrolimus ointment resulted in anti-inflammatory effect on the LPR during anti-IgE-mediated hypersensitivity. Several uncontrolled studies and randomized, placebo-controlled trial in adult and pediatric patients with moderate-to-severe AD have reported that treatment with topical tacrolimus results in markedly diminished pruritus and skin inflammation (1,4).
후속연구
Therefore, it can be indicated the interaction between MCs and EPs exacerbate the magnitude of disease activity. Further studies are needed to confirm the correlation between repeated exposure like allergen or microbial antigen and the severities degrees of the lesion or the magnitude influx of EP infiltration.
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