IN-SITU CHARACTERIZATION OF INFLAMMATORY RESPONSES IN THE RECTAL MUCOSAE OF PATIENTS WITH SHIGELLOSIS

Shigella species cause bacillary dysentery in humans by invading epith elial cells of the colonic mucosa leading to colonic epithelial cell d estruction and inflammation. For further analysis of local gut inflamm ation, morphological changes and the potential involvement of mediator s in regulatory mechanisms of cell activation and cell proliferation w ere studied immunohistochemically in rectal mucosal biopsies taken fro m patients during the acute phase of shigellosis and at convalescence. Rectal biopsies from 25 Shigella dysenteriae-1 and 10 Shigella flexne ri-infected patients and from 40 controls were studied. The frequencie s of proliferative cells (Ki67-positive cells), p53-immunostaining cel ls, and cells coexpressing Ki67 with CD3 or with p53 were analyzed. Im munostaining for the inducible nitric oxide synthase (iNOS) and the en dothelial NOS was assessed. In addition, the frequencies of apoptotic cells and CD68(+) cells that engulf apoptotic cells were assessed. By morphological grading, 20% of the patients had advanced inflammation ( grade 3) in the acute phase; mild inflammation (grade 1) was seen in 3 7% of the patients at convalescence as well as in 10% of the controls. The findings in the present study suggest that in the acute phase of shigellosis inflammation is characterized by increased cell turnover i n the lamina propria (LP) and the epithelium, increased iNOS expressio n in the surface epithelium, and apoptosis, which seems to be associat ed,vith LP macrophages. The findings also suggest that neither p53 nor iNOS are important factors for the induction of apoptosis in shigello sis. Expression of p53 may be related to early cell activation in cryp t epithelium. Moreover, there is an indication of an active, low-level inflammatory process at convalescence. The results thus indicate that Shigella-induced inflammation is associated,vith a complex series of cellular reactions in the rectal gut mucosa which persist long after c linical symptoms have resolved.