Treatment of canine atopic dermatitis using exogenous cytokines

研究了犬特应性皮炎（AD）外周血单核细胞中白细胞介素4 (IL4) mRNA与γ干扰素（IFNg） mRNA的比值。在犬AD和人类中，细胞因子与Th2优势的不平衡与IFNg mRMA量的减少有关。在人AD中，Tb2显性的机制之一被认为是IFNg的缺乏和白细胞介素12受体β 2链的遗传异常。从体外给药IFNg，即使是短暂的，也可能改善IFNg的缺乏，从而改善Th1/Th2细胞因子的平衡，最终可能改善犬AD的临床症状。我们尝试给10只患有特应性皮炎的狗注射重组犬γ干扰素（rcIFNg），每周三次，持续两周。观察治疗前及两周临床体征改善情况、总IgE、竞争RT-PCR法检测IFNmRNA和IL4mRNA表达、皮肤活检及皮肤组织病理学、真皮肥大细胞计数。两周内，10只狗中有7只狗的临床症状得到改善，IFN/IL4细胞因子的比例增加，这表明犬特应性皮炎的外源IFN可能使细胞因子谱向Th1转移。注射后两周，所有10只狗的总IgE也有所下降，皮肤（棘皮）的厚度也有所下降。3只患者犬的IFN/IL4 mRNA比例未向Th2细胞因子转移，临床症状无明显改善。本研究提示，犬特应性皮炎患者给予rcIFNg可能通过改变Th2到Th1的细胞因子谱来改善临床症状。

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.