Study On The Prophylactic Therapeutic Effect Of γ-interferon On The Experimental Silicosis Of Rats

ObjectiveAccording to silicosis model of rats reproduced by intratracheal injection method, our experiment studied antagonistic mechanism of - interferon (IFN- ) against Interleukin -4( IL -4) and Transforming growth factor - 1 (TGF- 1) and the prophylactic therapeutic effect of - interferon on experimental silicosis of rats, to prove up a new approach of treating lung fibrosis.Methods1. Female Wistar rats all came from animal experimental ministry of China Medical University . Rats exposed to lower dose (20mg/rat) of quartz by intratracheal injection were divided into three groups randomly. They were saline normal control group , quartz exposed group, - interferon prophylactic treating group.2. 7 ~9 rats of each group were killed after the 1st month and 2nd month respectively. We measured changes of lung/body coefficient and hydroxyproline content of pulmonary tissue and observed pathomorphology of silicotic rats lung by use of HE and VG dyeing and expression of IL -4 and TGF - (31 by use of immunohistochemical technique and quantity analysis of protein expression by image analysis system.3. Statistical analysis methods we utilized were analysis of variance using SPSS10. 0 software and then significant difference was examined by Q test. Differences were considered to be significant at P <0.05.Results1. The changes of the lung/body coefficient of rats in quartz exposed groups were significantly higher than those of control groups at 1 and 2 months after instillation (P < 0.01). The changes of the lung/body coefficient of rats in - interferon treating groups were lower than those of quartz exposed groups, and higher than those of control groups at 1 and 2 months after instillation. However, these two results were both of no significance.2. The lung hydroxyproline contents in treated groups were significantly lower than those of quartz exposed groups at 1 and 2 months after instillation ( P< 0.05). The lung hydroxyproline in treated groups were higher than those of control groups especially at 1 month (P<0.05).3. The fibrotic degree in silicotic lesions of rat lung was much lighter in IFN - -y treated groups than that of quartz groups, and lighter 1/2 ~ 1 grade.4. Quantity image analysis showed that from 1 month to 2 months after instillation , integrated OD total of IL - 4 positive cell in quartz exposed and IFN -"y treated groups was decreased, and that of TGF - Bl positive cell was increased. The integrated OD totals of IL -4 and TGF - pi positive cell in IFN -"y treated group were lower than those of quartz exposed group, and the differences were of significance (P <0. 05 or P <0.01).DiscussionIn the past several years, there were important improvements in the researches of mechanism of lung fibrosis. Especially many kinds of cells and cytokines in the lung played an important role in this complex process, thereby the conceptions of I type and E type cytokines were put forward.IFN - -y was prototypic type I cytokine, secreted by lymphocytes and nature killing cells, and had strong immunoregulatory effect, considered as potential anti - fibrotic effect. Its possible mechanism included: (1) anti - fibrogenic activity of type II cytokines, IL -4 for example; (2)anti - collegenous effect ofTGF - 1; (3) inhibit collegenation of fibroblasts. Type II cytokines and TGF -1 play a critical role in the pathogenesis of lung fibrosis through stimulation of collagen and fibronectin production in fibroblasts.Our experiments observed the prophylactic therapeutic effect of IFN - on silicotic lung of rats for 1 and 2 months. The results showed that the hydroxypro-line content in IFN - -y treating groups were significantly lower than that of quartz exposed groups at 1 and 2 months after instillation. Pathologic sections revealed that the fibrotic degree in IFN - y treating group was obviously lighter than that of quartz group. We might conclude that IFN - -y could reduce the hydroxyproline content in silicotic lung, and it might have some antagonist...