YOKOO Akifumi Sapporo Medical University School of Medicine Clinical Instructor, 医学部, 助手 (90244368)
南部 明民 札幌医科大学, 医学部, 助手 (60244357)
三熊 直人 札幌医科大学, 医学部, 助手 (30190614)
塚本 泰司 札幌医科大学, 医学部, 教授 (50112454)
SATOH Takashi Sapporo Medical University School of Medicine Clinical Instructor, 医学部, 助手 (00244351)
岩澤 晶彦 札幌医科大学, 医学部, 助手
NISHIMURA Masahiro Sapporo Medical University School of Medicine Clinical Instructor, 医学部, 助手 (10208225)
IWASAWA Akihiko Sapporo Medical University School of Medicine Clinical Instructor
|Budget Amount *help
¥7,800,000 (Direct Cost : ¥7,800,000)
Fiscal Year 1997 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 1996 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Fiscal Year 1995 : ¥4,500,000 (Direct Cost : ¥4,500,000)
We studied the local immune responses in a mouse experiment with acute ascending pyelonephritis. The experimental infections were induced in BALB/c female mice by transurethral instillation of E.Coli or P.aeruginosa.
In the normal mice having no evidence of the infection, mucosa associated lymphoid tissue (MALT) consisted of macrophages, la-positive cels and T cels (CD4, CD8 and gamma/delta) was visible in the pelvic mucosa. Ia-positive cells, macrophages, neutrophils, T cells were significantly infiltrated in the renal pelvic mucosa from 6 hours after bacterial inoculation. Then, IgA-positive B cells were infiltrated from 24 hours after inoculation. Therefore, it is possible that T cells play an active immune regulatory role in the early inflammatory phase against bacterial infections.
Various compromised host models were created in mice for use in local immune response of pyelonephritis. In the impaired neutrophilic chemotaxis hosts, the response of macrophages and CD4-T cells were enh
anced, and infltration of IgG-positive B cells during the early inflammatory phase was decreased, and there was accompanying weakening of the B cell response. However, the neutrophil response was found to be enhanced. In the diabetic hosts, the infiltration of T cells was decreased and accompanying weakening of the B cell response was noted. On the bases of the above findings, it was found that the response of cells involved in immunity varies as a function of modification of the defenses against infections, ant there is a possibility of compensatory responses.
Next, we studied the effects of BRM to immune response on urinary tract in compromised hosts. In the impaired T cell function hosts, it was found the IL-2 or IFN-gamma restored to the impaired T and B cell responses. However, TNF-alpha was not found any effects on their responses. In the diabetic hosts, and BRMs such as IL-2, G-CSF and TNF-alpha were not effective on the impaired local immune responses.
Lastly, we studied the relationship with gene expression of inflammatory cytokines or expression of cell adhesion molecules, and the local immune responses. It is possible that local immune responses were regulated with time by inflammatory cytokines and cell adhesion molecules. Less