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The purpose of this study was to evaluate a combination of immunostimulatory bacterial DNA sequences and allergen-specific immunotherapy for the treatment of canine atopic dermatitis. Seven dogs with nonseasonal atopic dermatitis diagnosed by history, clinical signs and exclusion of differential diagnoses were included. All dogs had been on allergen-specific immunotherapy for at least 12 months with incomplete responses, were on additional antipruritic therapy and showed residual pruritus. Pruritus was marked by the owner on a visual analogue scale, lesions were determined by a clinician using the Canine Atopic Dermatitis Extent and Severity Index (CADESI), and concurrent medications were recorded before entering the study and after 14 weeks of treatment. Peripheral blood mononuclear cells were isolated and cultured; canine cytokine message for IFNγ, IL-4, TNF and IL-10 was quantitated using RT-PCR. A mixture of allergen extract and liposome-DNA complexes was injected intradermally at the beginning of the study and after 2, 4, 6, 10 and 14 weeks. CADESI, pruritus and medication scores, and cytokine messages at the beginning and end of the study were compared with a paired t -test. There were significant improvements in pruritus scores ( P = 0.0277). Reductions in medication scores and CADESI were not statistically significant. IL-4 production decreased significantly ( P = 0.0428); decreases in other cytokines were not significant. Although the number of dogs in this pilot study was small, the results warrant further investigation of a combination of immunostimulatory bacterial DNA sequences and allergen-specific immunotherapy for the treatment of canine atopic dermatitis.
Funding: Self-funded. 相似文献
Funding: Self-funded. 相似文献
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Erin E. McCandless Catherine A. Rugg Gregory J. Fici James E. Messamore Michelle M. Aleo Andrea J. Gonzales 《Veterinary immunology and immunopathology》2014,157(1-2):42-48
The canine cytokine IL-31 induces pruritus in dogs and can be detected in dogs with atopic dermatitis; however very little is understood around its interactions with specific canine cells. We hypothesize that IL-31 is involved in the progression of allergic skin disease by coordinating the interaction between the immune system with skin and neuronal systems. The goal of the following work was to identify cells that produce IL-31 as well as cells that may respond to this cytokine. Peripheral blood mononuclear cells (PBMCs) were collected from naïve and house dust mite (HDM) allergen-sensitized beagle dogs and used for ex vivo characterization of cytokine production assessed using ELISpot and quantitative immunoassay. Sensitization to HDM allergen induced a T-helper type 2 (Th2) cell phenotype characterized by an increase in the production of IL-4 protein. Interestingly, repeated allergen challenge over time also resulted in an increase in IFN-γ. Further evaluation showed that co-stimulation of Th2 polarized cells with antigen and the bacterial component Staphylococcus enterotoxin B (SEB) produced higher levels of IL-31 compared to either stimulant alone. Production of IL-31 when PBMCs were stimulated by T cell mitogens suggests T cells as a source of IL-31. Quantitative real-time PCR was utilized to determine expression of the IL-31 receptor alpha chain in canine cell lines and tissue. Canine monocytic cells, keratinocytes, and dorsal root ganglia were shown to express the IL-31 receptor alpha chain mRNA. In a multifaceted disease such as canine atopic dermatitis, the combination of Th2 polarization and microbial presence may lead to IL-31 mediated effects driving inflammation and pruritus by immune cells, keratinocytes, and direct neuronal stimulation. 相似文献
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The purpose of this study was to evaluate a combination of immunostimulatory bacterial DNA sequences and allergen‐specific immunotherapy for the treatment of canine atopic dermatitis. Seven dogs with nonseasonal atopic dermatitis diagnosed by history, clinical signs and exclusion of differential diagnoses were included. All dogs had been on allergen‐specific immunotherapy for at least 12 months with incomplete responses, were on additional antipruritic therapy and showed residual pruritus. Pruritus was marked by the owner on a visual analogue scale, lesions were determined by a clinician using the Canine Atopic Dermatitis Extent and Severity Index (CADESI), and concurrent medications were recorded before entering the study and after 14 weeks of treatment. Peripheral blood mononuclear cells were isolated and cultured; canine cytokine message for IFNγ, IL‐4, TNF and IL‐10 was quantitated using RT‐PCR. A mixture of allergen extract and liposome‐DNA complexes was injected intradermally at the beginning of the study and after 2, 4, 6, 10 and 14 weeks. CADESI, pruritus and medication scores, and cytokine messages at the beginning and end of the study were compared with a paired t‐test. There were significant improvements in pruritus scores (P = 0.0277). Reductions in medication scores and CADESI were not statistically significant. IL‐4 production decreased significantly (P = 0.0428); decreases in other cytokines were not significant. Although the number of dogs in this pilot study was small, the results warrant further investigation of a combination of immunostimulatory bacterial DNA sequences and allergen‐specific immunotherapy for the treatment of canine atopic dermatitis. Funding: Self‐funded. 相似文献
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Allergen challenge decreases mRNA expression of regulatory cytokines in whole blood of high-IgE beagles 总被引：1，自引：0，他引：1
The kinetics of cytokine expression was evaluated in whole blood from high-IgE beagles previously sensitized to house dust mites (HDM) and known to develop clinical signs compatible with atopic dermatitis (AD) upon allergen exposure. Six high-IgE beagles were environmentally challenged daily for 3 h on three consecutive days with a HDM solution. Clinical signs were evaluated before, during, and after the conclusion of the challenge (days 0, 2, 4 and 17) and expression analyses of Th2 (IL-4 and IL-13) and regulatory (IL-10 and TGF-beta) cytokine mRNA were undertaken on blood samples at each time point using real-time polymerase chain reaction. Multiple comparison used to detect significant differences in clinical scores and expression levels of cytokine mRNA revealed that the clinical scores on days 2 and 4 were higher than those on days 0 and 17 (P < 0.05) but no temporal differences in the expression levels of IL-4 and IL-13 mRNA. Expression of TGF-beta mRNA was, however, significantly lower on day 4 (P < 0.05) and the expression of IL-10 mRNA on days 4 and 17 was significantly lower than those on days 0 and 2 (P < 0.05). The results indicate that allergen challenge decreases mRNA expression of regulatory cytokines in whole blood without enhanced mRNA expression of Th2 cytokines and suggest aberrant regulatory T-cell function in the immunopathogenesis of AD in high-IgE beagles. 相似文献
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The classical treatments for dogs with atopic dermatitis have traditionally been oral antipruritic drugs, allergen-specific immunotherapy and topical therapy. Fifty dogs with atopic dermatitis were included in this multicentred, double-blinded, randomized study to compare clinical response to an 8-week period of feeding one of three commercial veterinary foods marketed for dogs with atopic dermatitis (diets A-C) or a widely distributed supermarket food (diet D). Atopic dermatitis was diagnosed using Willemse's criteria and through the exclusion of differential diagnoses. Fourteen dogs were assigned to diet A and 12 dogs each to diet B, C or D. Flea and tick control using a monthly fipronil spot-on product was administered for a minimum of 4 weeks prior to inclusion in the study and during the study period. Evaluations were made monthly. These included lesion scores, using an established scoring system (canine atopic dermatitis extent and severity index, CADESI-03) and owner evaluation of pruritus level using a visual analogue scale. After 8 weeks on the new diets, there was a significant improvement in CADESI and pruritus scores with diet B (Wilcoxon test, P = 0.043 and paired t-test, P = 0.012, respectively), in pruritus scores with diet A (paired t-test, P = 0.019) and in CADESI scores with diet D (Wilcoxon test, P = 0.037). No significant changes were detected with diet C. Based on the results of this study, in addition to the conventional therapies, changing the diet of dogs with atopic dermatitis may be a useful adjunctive therapeutic measure. 相似文献
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Takuya Mizuno Satoshi Kanbayashi Takumi Okawa Sadatoshi Maeda Masaru Okuda 《Veterinary immunology and immunopathology》2009,131(1-2):140-143
The newly discovered cytokine, interleukin-31 (IL-31), belongs to the short-chain cytokine group. It was reported that transgenic expression of IL-31-induced pruritus, similar to atopic dermatitis, in mice, further, excessive amounts of IL-31 was also expressed in the skin from human patients with atopic dermatitis as compared to that from normal people. In this study, canine IL-31 was molecularly cloned from concanavalin A-stimulated canine peripheral blood mononuclear cells (PBMCs), and its nucleotide sequence was determined. Canine IL-31 contains 4 alpha-helix structures characteristic of the IL-31 family, and the amino acid identity of canine IL-31 with those of human or mouse is 54% and 28%, respectively. Furthermore, we detected low levels of canine IL-31 in the thymus, testis, spleen, and kidneys, but not in the skin of atopic dogs. 相似文献
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Atopic dermatitis (AD) is thought to be caused by immunologic abnormalities expressed as a Th1/Th2 cytokine imbalance in both humans and dogs. Several studies have focused on the therapeutic effects of IFNγ in human AD with successful results; however, the mechanism of action of IFNγ is not fully understood. We investigated the effect of recombinant canine interferon gamma (rCaIFNγ) on 10 dogs with AD and evaluated the ratio of IL-4 mRNA to IFNγ mRNA in peripheral blood mononuclear cells, serum total IgE levels, and histological changes in skin. After six injections of rCaIFNγ over a span of 2 weeks, seven of the 10 dogs showed improvement, and six of these seven dogs exhibited decreased IL-4:IFNγ mRNA ratios. Two of the three cases that did not improve had increased IL-4:IFNγ mRNA ratios. Total serum IgE levels were significantly decreased in nine of 10 cases. The number of IgE-positive cells detected by immunostaining and the number of mast cells in skin biopsy samples were decreased. A reduction of epidermal cell layers was demonstrated by histopathology after treatment. These results demonstrated that rCaIFNγ may be a novel safe and effective therapeutic option for the treatment of canine AD, and the mechanism of action of rCaIFNγ may be related to the modulation of Th2 cytokines to Th1 cytokines with the reduction of serum IgE production.
Funding: Self-funded. 相似文献
Funding: Self-funded. 相似文献
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The dog is the main reservoir of Leishmania infantum, the parasite responsible for visceral leishmaniasis in Mediterranean countries. The infection in dogs shows different clinical presentations, from subclinical/asymptomatic to a fully developed disease, depending on the host's immune responses. The Th1/Th2 dichotomy is not clear in the different forms of canine leishmaniasis, since the data available from studies of immunity response in canine leishmaniasis are scarce and fragmented. The present work describes the cytokine expression in peripheral blood mononuclear cells (PBMC) obtained from asymptomatic dogs experimentally infected with L. infantum that present a cellular protective immune response. The results obtained from freshly isolated PBMC showed expressions of TNF-alpha, IL-2, IFN-gamma, IL-10 and IL-18 mRNA, similar to those from non-infected dogs. However, there was almost no expression of IL-4 mRNA detected in the asymptomatic infected dogs compared to the control dogs. Unspecific stimulation with ConA promoted the expression in a greater or lower degree of all the cytokines studied. In vitro stimulation of PBMC with soluble leishmanial antigen (SLA) promoted the expression of IL-2, IFN-gamma, TNF-alpha, IL-18, IL-4, IL-6 and IL-10 mRNA, with the two first being specifically induced. Although both Th1 and Th2 cytokines are produced, cell mediated immunity observed in these L. infantum-infected asymptomatic dogs depended on the preferential expression of Th1 cytokines. 相似文献
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Seven dogs with atopic dermatitis and six normal dogs were treated with a spot-on product containing essential oils and unsaturated fatty acids q 7 days for 8 wk. Seven additional atopic dogs received a daily spray containing similar ingredients to the spot-on. In all dogs, transepidermal water loss (TEWL) was measured before and after treatment using a closed chamber device. In atopic dogs, a validated lesion score (canine atopic dermatitis extent and severity index, CADESI) was determined and pruritus was assessed with a visual analog scale before and after treatment. The mean CADESI scores in atopic dogs decreased with the spot-on (P=0.0043) and with the spray (P=0.0366). Similarly, the pruritus scores decreased with the spot-on (P=0.266) and with the spray (P=0.0177). There was a significant difference between the TEWL values of healthy and atopic dogs on the abdomen (P=0.0181) and back (P=0.0123). TEWL decreased significantly on the back after treatment with the spray (P=0.016), but not on the abdomen (P=0.078). Adverse effects were not observed. The results of this pilot study indicate that topical fatty acids and essential oils are a useful treatment option for canine atopic dermatitis. 相似文献
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The molecular and immunologic mechanisms associated with successful allergen-specific immunotherapy (ASIT) have not been completely elucidated. The aim of this study was to characterize the changes in Dermatophagoides farinae -specific IgG in atopic dogs undergoing ASIT using aqueous vaccines. Fifteen atopic dogs with a positive skin test reaction to D. farinae were treated with aqueous vaccines for a minimum of 2 months following a standard protocol. Serum samples were collected before and during therapy and used to probe Western blots containing separated proteins of D. farinae . IgG responses were detected using a polyclonal goat anticanine IgG antibody and a chromogenic substrate 3,3'-diaminobenzidine. The blots were analysed using a semiquantitative digital image analysis system that evaluated the number and molecular weight of bands, as well as their intensity, which was related to IgG concentration. Prior to ASIT, all dogs showed allergen-specific IgG responses to various antigens of D. farinae . During ASIT, there was a significant increase in the total quantity of D. farinae -specific IgG antibodies to various antigens from the mite ( P = 0.015). Significant increases were observed for a 98-kDa band ( P = 0.015), likely to be Der f 15; bands with molecular weights between 50 and 70 kDa ( P = 0.012); and bands between 30 and 45 kDa ( P = 0.035). These findings provide support for the hypothesis that ASIT induces IgG blocking antibodies to allergens known to be relevant in canine atopic dermatitis. 相似文献
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OBJECTIVE: To evaluate the safety of an abbreviated course of injections of allergen extracts (rush immunotherapy) for the treatment of dogs with atopic dermatitis. ANIMALS: 30 dogs with atopic dermatitis examined at a veterinary dermatology referral practice for treatment with allergen-specific immunotherapy. PROCEDURE: A catheter was placed in a vein in each dog. Dogs were constantly observed throughout the procedure. Allergen extracts were administered in increasing concentrations every 30 minutes for 6 hours to a maintenance concentration of 20,000 protein nitrogen units/ml. Epinephrine, oxygen, and emergency treatment were available as needed. RESULTS: In 22 (73%) dogs, rush immunotherapy safely replaced the prolonged induction period (15 weeks) of weekly injections that consists of increasing concentrations of allergen extract. In 7 (23%) dogs, the induction period was abbreviated to 4 weeks. Of the 8 dogs that developed problems during rush immunotherapy, increased pruritus necessitated premature cessation of rush immunotherapy in 7, and 1 developed generalized wheals. Oral administration of prednisolone (1 mg/kg of body weight) resulted in resolution of adverse effects in all 8 dogs. CONCLUSION AND CLINICAL RELEVANCE: Rush immunotherapy performed by personnel at a veterinary hospital is a safe method for treatment of dogs with atopic dermatitis. 相似文献
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Wuersch K Brachelente C Doherr M Reist M Sattler U Forster U Bertoni G Peel JE Welle M 《Veterinary immunology and immunopathology》2006,110(3-4):311-323
BACKGROUND: Flea allergy dermatitis (FAD) is a common skin disease in dogs and can be induced experimentally. It often coexists with other allergic conditions. So far no studies have investigated the quantitative production of cytokine mRNA in skin biopsies and peripheral blood mononuclear cells (PBMC) in flea allergic dogs. OBJECTIVE: The aim of our study was to improve the understanding of the immunopathogenesis of allergic dermatitis as a response to fleabites. MATERIAL AND METHODS: Allergic and non-allergic dogs were exposed to fleas. Before and after 4 days of flea exposure mRNA was isolated from biopsies and PBMC. Production of chymase, tryptase, IL-4, IL-5, IL-13, TNF-alpha and IFN-gamma mRNA was measured by real-time RT-PCR. The inflammatory infiltrate in the skin was scored semi-quantitatively. The number of eosinophils, mast cells (MC) and IgE+ cells/mm2 was evaluated to complete the picture. RESULTS: FAD was associated with a higher number of MC before flea exposure and with a significant increase of eosinophils after flea exposure as compared to non-allergic dogs. The number of IgE+ cells was higher in allergic dogs before and after flea exposure. In allergic dogs mRNA for most cytokines and proteases tested was higher before flea exposure than after flea exposure. After exposure to fleas an increased mRNA production was only observed in non-allergic dogs. In vitro stimulation with flea antigen resulted in a decreased expression of most cytokines in allergic dogs before flea exposure. In contrast, in PBMC, only increased levels of IL-4 and IL-5 mRNA were observed in allergic dogs before flea exposure. However, after flea exposure and additional stimulation with flea antigen the production of mRNA for all cytokines tested was significantly increased in allergic dogs. CONCLUSION: We demonstrated that the response in biopsies and PBMC is different and that FAD is associated with a TH2 response. 相似文献
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Sipos W Duvigneau JC Pietschmann P Schilcher F Hofbauer G Hartl RT Schmoll F 《Veterinary immunology and immunopathology》2005,107(3-4):303-313
Porcine dermatitis and nephropathy syndrome (PDNS) is broadly discussed as a porcine circovirus type 2 (PCV2)-associated disease, although PCV2, in contrast to postweaning multisystemic wasting syndrome (PMWS), has to date not been proven to be the aetiologic agent. In order to better understand the complex immunopathology of PDNS, the systemic cytokine expression profiles of (i) five pigs suffering from PDNS, (ii) five animals suffering from naturally acquired PMWS and (iii) five controls were investigated at mRNA and protein levels by means of multiplex real-time RT-PCR and flow cytometric intracellular cytokine detection, respectively. IL-1alpha, IL-6 and IFN-gamma mRNA expressions were found to be elevated in PDNS pigs. At the protein level, an increased capacity of peripheral blood mononuclear cells to produce IL-2, IL-4, IL-6, IL-12, TNF-alpha and IFN-gamma was evident. Hematological investigations revealed a hypochromic anemia while basophils and monocytes were relatively and neutrophils absolutely increased in PDNS pigs. PCV2 antibody levels did not differ significantly between PDNS and PMWS affected animals. Taken results together, the cytokine profile of the PDNS affected animals together with hematological data pointed towards a proinflammatory condition supporting a Th1 bias. Cytokine data of PMWS affected animals exhibited only minor non-significant differences when compared to controls, only IL-10 was significantly decreased at the mRNA level. 相似文献