Alimentary TractSubtherapeutic corticosteroids potentiate the ability of interleukin 10 to prevent chronic inflammation in rats☆,☆☆,★
Section snippets
Animals and reagents
Female, inbred, specific pathogen–free Lewis rats (145-155 g) were obtained from Charles River Laboratories (Raleigh, NC). Rats were fed Agway Prolab rat chow (Agway Inc., Syracuse, NY) ad libitum and were weighed daily. All rat experiments were conducted in accord with the highest standards of humane animal care as outlined in the National Institutes of Health's “Guide for the Care and Use of Laboratory Animals” and were approved by the University of North Carolina Institutional Animal Care
The effects of IL-10 and DEX on IL-1 and IL-1RA in vitro
To investigate whether the combination of IL-10 and DEX would exceed the anti-inflammatory potential of either agent alone, we first determined the effects of these drugs on the IL-1RA/IL-1β ratio in supernatants of LPS-stimulated human PBMNCs (Figure 1).
Discussion
We show in this study that IL-10 and DEX have additive anti-inflammatory effects in vivo and in vitro. In agreement with our recently published results,17 pretreatment with high doses of IL-10 alone completely prevented arthritis and significantly attenuated intestinal granulomatous inflammation. The combination of IL-10 and DEX is clinically relevant, because corticosteroids are an important mainstay of IBD therapy18 and intravenous IL-10 was effective in a small trial of patients with
Acknowledgements
The authors thank Roger Brown for preparation of PG-APS, Julie Vorobiov and Lisa Holt for technical support, and Susie May and Beverly Vought for secretarial assistance.
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Cited by (44)
Immunomodulatory effects of Bifidobacterium bifidum 231 on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats
2017, Research in Veterinary ScienceCitation Excerpt :TNF-α seems to play a major role in the duration of inflammation in Crohn's disease. IL-10 is regarded as a very important immunoregulatory and contra-inflammatory cytokine, which exerts its anti-inflammatory effects by suppressing the production of inflammatory proteins, including IL-1β and TNF-α (Herfarth et al., 1998). Free radicals are produced in patients affected with IBD and it is evident from previous studies that demonstrated the production of free radicals from blood monocytes (Kitahora et al., 1988) and intestinal macrophages (Rugtveit et al., 1995).
Protective effect of Lactobacillus plantarum 21, a probiotic on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats
2015, International ImmunopharmacologyCitation Excerpt :TNF-α stimulate and induce the production of other inflammatory mediators such as reactive oxygen species (ROS), and it also activates oxidative stress-responsive genes which amplify and prolong inflammation [6]. IL-10 is regarded as a very important immunoregulatory and contra-inflammatory cytokine, which exerts its anti-inflammatory effects by suppressing the production of inflammatory proteins, including TNF-α [7]. Excessive production of ROS in mucosal cells induced inflammatory and immune responses which could directly or indirectly cause damage of intestinal epithelial cells, subsequently influence mucosal integrity or initiate an inflammatory signaling cascade and lead to severe impairment in experimental colitis.
Ryanodine Receptor Antagonism Protects the Ischemic Liver and Modulates TNF-α and IL-10
2007, Journal of Surgical ResearchCitation Excerpt :The data from investigations on the effects of IL-10 on immune cells and animal models suggests that the major physiological importance of IL-10 seems to be the limitation of inflammation, the prevention of uncontrolled nonadequate immunological reactions, as well as the support of the humoral (Th2) immune responses [32, 33]. This hypothesis was confirmed by experimental research in animals, including analyses of IL-10 knockout mice as well as by the effects of IL-10 observed in several inflammatory, autoimmune, and tumor models [34–42]. Other studies similar to ours that directly determined the production of IL-10 in a typical model of mouse liver I/R have not been introduced, even though it has been carried in hepatocyte cultures.
Anti-Ischemic Effect of Selectin Blocker Through Modulation of Tumor Necrosis Factor-α and Interleukin-10
2007, Journal of Surgical ResearchCitation Excerpt :The results of these studies clearly showed prevention of intestinal inflammation by IL-10, mainly by down-regulation of an intestinal proinflammatory Th1-like response [39]. However, systemic IL-10 administration was successful only when administered before the initiation of colitis but was ineffective at reversing any established inflammation [40–43]. Effects of IL-10 application have been investigated in various other inflammatory animal models, as well.
Timing of pentoxifylline treatment determines its protective effect on diabetes development in the Bio Breeding rat
2002, European Journal of Pharmacology
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Address requests for reprints to: R. Balfour Sartor, M.D., Division of Digestive Diseases & Nutrition, UNC School of Medicine, Room 030 Glaxo Building, CB 7080, Chapel Hill, North Carolina 27599-7080. e-mail: [email protected]; fax: (919) 966-7468.
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Supported by grants He 2379/1-1 and Bo1340/1-1 from the Deutsche Forschungsgemeinschaft, the National Institutes of Health grants DK 40249 and DK 34987, and Schering-Plough Research Institute.
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Dr. Herfarth's current address is: Klinik and Poliklinik für Innere Medizin I, Universität Regensburg, Germany.