Treatment of canine atopic dermatitis using exogenous cytokines

研究了特应性皮炎（AD）犬外周血单个核细胞（PBMC）中白细胞介素4（IL 4）mRNA与γ干扰素（IFNg）mRNA的比值。在人和犬AD中均发现了细胞因子对Th 2优势的失衡和IFNg mRMA的减少，在人AD中Tb 2优势的机制之一被认为是IFNg的缺乏，并有报道白细胞介素12受体β 2链的遗传异常。当IFNg从体外给药时，IFNg的缺乏可能得到改善，即使是短暂的，这可能会改善Th 1/Th 2细胞因子平衡，最终可能改善犬AD的临床症状。我们尝试将重组犬干扰素γ（rcIFNg）给药于共10只特应性皮炎犬，每周3次，持续2周。治疗前和治疗后2周观察临床症状改善情况、总IgE、竞争性RT-PCR法检测IFN mRNA和IL 4 mRNA表达、皮肤活检和皮肤组织病理学检查、皮肤肥大细胞计数，结果显示，rcIFNg治疗后2周内10只犬中有7只犬临床症状改善，IFN/IL 4比值升高，表明外源性IFN对犬特应性皮炎的作用可能使细胞因子谱向Th 1型转变。注射后两周，所有10只犬的总IgE也降低，皮肤厚度（棘皮病）程度降低。3只患犬IFN/IL 4 mRNA比值未向Th 2型细胞因子转变，临床症状无明显改善，提示rcIFNg治疗特应性皮炎可能通过改变Th 2型细胞因子向Th 1型细胞因子转变而改善临床症状。

The ratio of interleukin 4 (IL4) mRNA versus gamma interferon (IFNg) mRNA in PBMC (peripheral blood monocytes) of canine atopic dermatitis (AD) was studied. Imbalance of cytokine to Th2 dominance with the decreased amount of IFNg mRMA was found in canine AD as well as human.In human, the one of the mechanism of Tb2 dominance in AD was thought to be the paucity of IFNg and the genetic abnormality in interleukin 12 receptor beta2 chain was reported. When the IFNg is administered from the outside of the body, the paucity of IFNg might be improved even it is transiently, which may improve the Th1/Th2 cytokine balance, finally, it is possible to improve file clinical signs of canine AD.We tried to administer the recombinant canine interferou gamma (rcIFNg) to total of ten dogs with atopic dermatitis three times a week for two weeks aubcutaneously. The improvement of clinical signs, total IgE, the expression of IFNmRNA and IL4mRNA by the competitive RT-PCR method, skin biopsies and cutaneous histopathology, dermal mast cell counts were performed at before and two weeks.Dog patients administered the rcIFNg improved their clinical signs in seven out of ten dogs within two weeks with the increase of the ratio of IFN/IL4 cytokines, which indicated that the outgenous IFN to the canine atopic dermatitis may shift the cytokine profile to Th1. Total IgE also decreased in all ten dogs and the degree of thickness of the skin (acanthosis) decreased two weeks after the injection. IFN/IL4 mRNA ratio did not shift to Th2 cytokines in three patient dogs with no apparent improved clinical signs.This study indicates that the adminiatration of rcIFNg to the dog patients with atopic dermatitis may improve the clinical signs by the alteration of cytokine profile from Th2 to Th1.