BACKGROUND & AIMS: Interleukin (IL)-10, which inhibits macrophages and T-helper lymphocyte type 1 (TH1) lymphocytes, attenuates chronic granulomatous inflammation induced by bacterial cell wall polymers. This study determines whether corticosteroids enhance the protective effects of IL-10 in cultured peripheral blood mononuclear cells (PBMNCs) and in vivo when started before or after the onset of experimental chronic granulomatous inflammation. METHODS: Intestines of Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Daily murine recombinant IL-10 and/or dexamethasone (DEX) therapy was started 12 hours before or at several intervals after PG-APS injection. RESULTS: IL-10 plus corticosteroids additively inhibited IL-1beta secretion in human PBMNCs but preserved the beneficial IL-1RA/IL-1beta ratio induced by IL-10. IL-10 started before PG-APS injection significantly attenuated intestinal and extraintestinal inflammation, with even more pronounced effects in combination with subtherapeutic doses of DEX. The combination of DEX decreased the effective dose of IL-10 by at least one half. After onset of systemic inflammation using doses effective for prevention, IL-10 monotherapy had nearly no benefit and DEX plus IL-10 was similar to the mild therapeutic effect of DEX alone. CONCLUSIONS: The combination of IL-10 and corticosteroids allows lower doses of both agents in preventing chronic intestinal and systemic inflammation. However, timing of IL-10 administration is a critical variable in regulating inflammation.
BACKGROUND & AIMS:Interleukin (IL)-10, which inhibits macrophages and T-helper lymphocyte type 1 (TH1) lymphocytes, attenuates chronic granulomatous inflammation induced by bacterial cell wall polymers. This study determines whether corticosteroids enhance the protective effects of IL-10 in cultured peripheral blood mononuclear cells (PBMNCs) and in vivo when started before or after the onset of experimental chronic granulomatous inflammation. METHODS: Intestines of Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Daily murine recombinant IL-10 and/or dexamethasone (DEX) therapy was started 12 hours before or at several intervals after PG-APS injection. RESULTS:IL-10 plus corticosteroids additively inhibited IL-1beta secretion in human PBMNCs but preserved the beneficial IL-1RA/IL-1beta ratio induced by IL-10. IL-10 started before PG-APS injection significantly attenuated intestinal and extraintestinal inflammation, with even more pronounced effects in combination with subtherapeutic doses of DEX. The combination of DEX decreased the effective dose of IL-10 by at least one half. After onset of systemic inflammation using doses effective for prevention, IL-10 monotherapy had nearly no benefit and DEX plus IL-10 was similar to the mild therapeutic effect of DEX alone. CONCLUSIONS: The combination of IL-10 and corticosteroids allows lower doses of both agents in preventing chronic intestinal and systemic inflammation. However, timing of IL-10 administration is a critical variable in regulating inflammation.
Authors: J F Colombel; P Rutgeerts; H Malchow; M Jacyna; O H Nielsen; J Rask-Madsen; S Van Deventer; A Ferguson; P Desreumaux; A Forbes; K Geboes; L Melani; M Cohard Journal: Gut Date: 2001-07 Impact factor: 23.059
Authors: Phyllissa Schmiedlin-Ren; Laura J Reingold; Christopher S Broxson; Ahren C Rittershaus; Josh S Brudi; Jeremy Adler; Scott R Owens; Ellen M Zimmermann Journal: Am J Physiol Gastrointest Liver Physiol Date: 2016-08-25 Impact factor: 4.052
Authors: Helene A Haeberle; Antonella Casola; Zoran Gatalica; Sharon Petronella; Hans-Juergen Dieterich; Peter B Ernst; Allan R Brasier; Roberto P Garofalo Journal: J Virol Date: 2004-03 Impact factor: 5.103