Naslov
The efect of azithromicin in a murine model of experimental colitis

Autori
Pleško, Sanja ; Banić, Marko ; Dohoczky, Cs. ; Plečko, Vanda ; Anić, B ; Brkić, Tomislav ; Kalenić, Smilja ; Rotkvić, Ivo ;

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book: Darmschleimhaut und Darmkrankenheit-Pathophysiologie und Klinik / Domschke W - Titisee-Neustadt : Falk Foundation e. V., 1999

Skup
Falk symposium No 110

Mjesto i datum
Titisee-Neustadt, Njemačka, 05.03.1998. - 07.03.1998

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Azithromicin; colitis

Sažetak
Background: In intestinal inflammation, the inflammatory cells accounting within mucosa and submucosa express various functional surface molecules including the receptor for IL-2 (CD 25). The aim of this study was to investigate the effect of cyclosporine (CsA), given intreperitonealy i.p.) or in a form of enema (i.r.) on number of CD25 plus inflammatory cells within colonic mucosa and submucosa, in haptene- induced murine model of experimental colitis. Methods: Experimental colitis was induced in NMRI mice (Pliva Research Institute), using the enema of 0.2 percent solution od Dinitrofluorobenzen (DNFB) (Sigma, Saint Luois, USA) in 4:1 acetone to olive solution, and combined with previous skin sensitisation. Two experimental groups of animals (N equal 6-8) were treated with 3/mg/kg/ day) of CsA diluted with phosponate buffered saline (PBS), and given i.p. or i.r., 6 hours after induction of colitis and for consecutive 5 days. One control group was treated with PBS i.r., in the same manner, after induction of colitis. Second control group consisted of untreated healthy animals. On day 5, all animals were killed and entire colon of each animal was longitudinally dissected in two halves that were taken for histology (HE) and immunohystochemical analysis for CD25 (anti mouse IL-2R/CD25, Boehringer Biochemica Mannheim, Germany), respectively. Colonic lesions were assessed using histopathologic score ranging 0-30, and mean number of CD25 plus cells in 20 HPF (light microscopy) from each specimen was expressed as mean plus (min SD for each group of animals). Results: CsA was effective in diminishing the histologic extent of provoked colonic inflammation in experimental groups treated with dose of 3 mg/kg/day i.p. or i.r. (p less 0.05, Kruskal-Wallkis, ANOVA). There was no difference between experimental groups in regard to way of application of CsA. Induction of experimental colitis significantly increased the number of CD25 plus inflammatory cells, when compared to mucosa of healthy animals (p less 0.05, Mann- Whitney). CsA , applied i.p. or i.r. significantly decreased the number of CD25 plus inflammatory cells, when compared to control group with experimental colitis, treated with PBS i.r. (p less 0.05, Mann-Whitney). There was no difference between experimental groups in regard to way of application of CsA (i.p. or i.r.). Conclusion: CsA in dose 3 mg/kg/day is capable of diminishing the extent of haptene induced colonic inflammation when applied i.p. or i.r.. This effect is in part expressed in decreasing the number of CD25 plus cells within colonic mucosa and submucosa. Background: anaerobic bacteria especially Bacteroides spp have been incriminated in the pathogenesis of experimental colitis in several animal models. The anti-inflammatory activity of azalides (as a subgroup of macrolide antibiotics) is recognised and documented in studies of in vivo models, and immunomodulation by antibiotic may anerge as an interesting aspect of therapy of intestinal inflammation. The aim of this study was to investigate the effect of azithromycin (as an azalide antibiotic) on inflammatory lesions in hapten-induced murine model for experimental colitis. Methods: Experimental colitis was induced in CD1 mice (Pliva research institute) using the enema of 0.2 percent solution of dinitroflourobenzene (DFNB) (Sigma, Saint Louis, USA) in 4:1 acetone to olive oil solution, and combined with previous skin sensitisation. Two experimental groups of animals (N=6-8 per group) were pre-treated with azithromycin 50 mg/kg/day (Sigma, Saint Louis, USA), respectively; starting 24 hours before induction of colitis with challenge enema of DNFB, and thereafter treated for consecutive 5 days. Other two experimental groups were also treated with same dose (50 mg/kg/day) of azithromycin or metronidazole, starting 6 hours after induction of colitis, and for 5 consecutive days. Substances were administratived after diluting with an equvivolume of phosphate buffered saline (PBS) and by means of oral lavage. One control group was treated with PBS only, i the same manner, starting 6 hours after induction of colitis. Second control group was treated with methylpredonisolone 10 mg/kg/day interperionealy, starting 6 hours after induction of colitis, and for 5 consecutive days. On day 5, all the animals were killed and entire colon of each animal was taken for histology (HE). Colonic lesions were assessed using histopathologic score ranging 0-30. Results: Azithromycin was effective in diminishing the histologic extent of provoked colonic inflammation in both, pre-treated group and in group which the treatment was started 6 hours after induction of colitis (p less then 0.05; Kruskal-Wallis ANOVA). The effect in both experimental group treated with azithromycin did not differ significantly when compared to anti-inflammatory effect in control group treated with metylprednisole. On the contrary, we observed no significant anti-inflammatory effect in groups treated with metronidazole when compared to maximal observed lesion in control group treated with PBS after induction of colitis. Conclusion: Azithromycin, applied with oral lavage in dose of 50 mg/kg/day, starting the treatment 24 hours before or 6 hours after induction of colitis, was shown to have significant anti-inflammatory effect in the range of methylpredonisolone. It seems unlikely that the effect of azithromycin in this particular model of experimental colitis could be attributed to its antimicrobial effect on intestinal flora.

Izvorni jezik
Engleski

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Javno zdravstvo i zdravstvena zaštita

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