The elucidation of pathogenesis with the experimental model of dry eye by IL-12 and IL-18 simultaneous administration

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671765
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: HYOGO COLLEGE OF MEDICINE
• Principal Investigator: KANNO Sanae HYOGO COLLEGE OF MEDICINE, OPHTHALMOLOGY, ASSISTANT PROFESSOR, 医学部, 講師 (10289069)
• Co-Investigator(Kenkyū-buntansha): OKAMURA Haruki HYOGO COLLEGE OF MEDICINE, LABORATORY OF HOST DEFENSES INSTITUTE FOR ADVANCED MEDICAL SCIENCES, PROFESSOR, 医学部, 教授 (60111043)
• Project Period (FY): 1999 – 2000
• Keywords: IL-18 / dry eye / apoptosis / mouse

Research Abstract

Whether the chronic inflammation appeared by applyingg eye drops of IL-12 and IL-18 simultaneously in the lacrimal gland of the mouse was examined. The invasion of the inflammatory cell was confirmed in a few mouse but in almost of the mouse of applying eye drops, the inflammation and apoptosis in the lacrimal gland was not hardly caused. Thus model mouse of dry eye, GVHD and Sjoegren syndrome could not be made.
The cytokine in mouse serum was measured. IL-18 was rosed within 6 days after, though IL-12 continuously rose after the instillation start. The movement of the blood cytokine equal to the one time in the peritoneal injection of IL-12 and IL-18. Though the movement of the serum cytokine is also same on the mouse which also injected the mouse which carried out the instillation, in the point that the change of the organization is not generated similarly, it was considered interesting. For more investigation we used the methos of peritoneal injection, and the experiment was carried out to be an acute mouse model.
We observed apoptosis in the lacrimal gland of the mouse of the acute model by the Tunel staining. All glandular epithelium cells of the lacrimal gland caused the apoptosis next day from IL-12 and IL-18 peritoneal injection, and small number of glandular epithelium cells caused the necrosis from the third day. Furthermore, epithelium cells returned in the normal glandular system proven after about 2 weeks. Serum cytokine of this time was measured by the ELISA method. The serum concentration of IFN-showed the peak value in 2-3 day, NO in 1-2 day, but IL-1, IL-6, IL-10 and TNF-could not recognize the change the peak. From the result using knockout-mouse, apoptosis of the lacrimal gland seem to be not system by Fas-FasR but apoptosis through NO.