Roth J A, Frank D E
Department of Veterinary Microbiology, Iowa State University, Ames 50011.
J Interferon Res. 1989 Feb;9(1):143-51. doi: 10.1089/jir.1989.9.143.
Three dosages (0.1, 0.5, and 2.5 mg/animal, subcutaneously), of recombinant bovine interferon-gamma (rBoIFN-gamma) were evaluated for their in vivo influence on neutrophil function and lymphocyte blastogenesis in cattle. The optimal of the three dosages tested (0.5 mg/animal or 1.1 x 10(6) U/animal) was then evaluated for its influence on neutrophils and lymphocytes in both normal and dexamethasone-treated cattle. One animal, which received 2.5 mg of rBoIFN-gamma, died by 24 h after administration due to acute diffuse interstitial pneumonia with interlobular edema and emphysema. The two highest dosages used caused fever at 24 h and the highest dosage caused a decrease in lymphocyte blastogenesis at 24 h after administration. The influence of rBoIFN-gamma on neutrophil function was dose dependent and depended on the baseline values for neutrophil function. Random migration by neutrophils was consistently inhibited in animals that received 0.5 mg or more of rBoIFN-gamma. Staphylococcus aureus ingestion and antibody-dependent cell-mediated cytotoxicity by neutrophils was enhanced by rBoIFN-gamma treatment in both dexamethasone-treated cattle and in nondexamethasone-treated cattle, which had relatively low values for these parameters before treatment. Iodination by neutrophils was also enhanced by rBoIFN-gamma when either a suboptimal concentration of neutrophil stimulant was used or when the cattle were treated with dexamethasone. In summary, the rBoIFN-gamma had greater immunomodulator activity in immunosuppressed than in normal cattle. The in vivo influence of rBoIFN-gamma therefore depends on the physiologic status of the animal.
对重组牛γ干扰素(rBoIFN-γ)的三种剂量(0.1、0.5和2.5毫克/动物,皮下注射)进行了评估,以研究其对牛中性粒细胞功能和淋巴细胞增殖的体内影响。然后对测试的三种剂量中的最佳剂量(0.5毫克/动物或1.1×10⁶单位/动物)进行评估,以研究其对正常和地塞米松处理的牛的中性粒细胞和淋巴细胞的影响。一只接受2.5毫克rBoIFN-γ的动物在给药后24小时因急性弥漫性间质性肺炎伴小叶间水肿和肺气肿死亡。所使用的两种最高剂量在给药后24小时引起发热,最高剂量在给药后24小时导致淋巴细胞增殖减少。rBoIFN-γ对中性粒细胞功能的影响呈剂量依赖性,并取决于中性粒细胞功能的基线值。在接受0.5毫克或更多rBoIFN-γ的动物中,中性粒细胞的随机迁移持续受到抑制。在经地塞米松处理的牛和未经地塞米松处理的牛中,rBoIFN-γ处理均增强了中性粒细胞对金黄色葡萄球菌的吞噬作用和抗体依赖性细胞介导的细胞毒性,这两种牛在处理前这些参数的值相对较低。当中性粒细胞刺激剂浓度次优或牛接受地塞米松处理时,rBoIFN-γ也增强了中性粒细胞的碘化作用。总之,rBoIFN-γ在免疫抑制的牛中比在正常牛中具有更大的免疫调节活性。因此,rBoIFN-γ的体内影响取决于动物的生理状态。