title: The dynamics of intestinal eosinophil depletion in rats treated with dexamethasone.
abstract: We examined the effects of corticosteroid treatment on eosinophils in the jejunal mucosa of rats previously infected with Nippostrongylus brasiliensis. Rats received a single intraperitoneal injection of 1 mg of dexamethasone. At a light microscopic level, the number of eosinophils with typical nuclei and granules was significantly decreased as early as 3 hours after injection, and had diminished to 17% of starting values at 24 hours. Pyknotic cells containing eosinophilic granules or fragments were observed scattered in the subepithelial interstitial space 3 and 7 hours after injection. By electron microscopy, more than 20% of eosinophils demonstrated nuclear abnormalities. Degenerating eosinophils without granular changes (27 of 127, 14.1%) or with or with granular changes (9 of 127, 7.1%) increased at 3 hours compared with untreated rats (8 of 233, 3.4%; 4 of 233, 1.7%). At 7 hours, 47 of 96 (49.0%) eosinophils were located inside phagocytic vacuoles of macrophages. Single macrophages occasionally engulfed two or more eosinophils. Only a few degeneration eosinophils (7 of 96) were observed outside macrophages. At 13 hours, the percentage of degenerating eosinophils and eosinophils inside macrophages was decreased; at 24 hours, few eosinophils were seen and eosinophil structures could not be identified inside macrophages. The epithelium and lamina propria did not show structural damage typical of an inflammatory reaction at any time. Eosinophil numbers in mesenteric lymph nodes, spleens, and peripheral blood were also reduced by dexamethasone. Similar observations were made in the jejunal mucosa of noninfected rats. We observed the slow restoration of eosinophil numbers in the intestinal wall, finally reaching preinjection numbers after 14 days. We conclude that dexamethasone has important effects on eosinophils causing (a) nuclear degeneration and (b) changes in the granular matrix. Subsequently, these damaged eosinophils are engulfed by macrophages and swiftly disappear from the intestinal mucosa. These effects appear to be due to the induction of apoptosis. Our findings offer an explanation for one of the significant antiinflammatory effects observed with the use of corticosteroids.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Kawabori
authors.forename: K
authors.initials: K
authors.lastname: Soda
authors.forename: M H
authors.initials: MH
authors.lastname: Perdue
authors.forename: J
authors.initials: J
authors.lastname: Bienenstock
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004802:Eosinophilia / Q000473:pathology / Q000503:physiopathology; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D007413:Intestinal Mucosa / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D007583:Jejunum / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D009349:Nematode Infections / Q000473:pathology* / Q000503:physiopathology; D009559:Nippostrongylus; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
chemical_list: D003907:Dexamethasone