Previous studies have shown the beneficial effects exerted by probiotics on inflammatory bowel disease(Reference Ewaschuk and Dieleman1), an intestinal condition characterized by an altered intestinal immune response(Reference Hanauer2). However, it would be interesting to know whether the immunomodulatory properties of probiotics are restricted to a local effect in the intestine or whether their effect can also be extrapolated to other systemic immune alterations. The aim of the present study was to test the effect of a probiotic, Lactobacillus salivarius CECT5713, in two experimental models of local or systemic altered immune response, i.e. the trinitrobenzenesulfonic acid (TNBS) model of rat colitis and the lipopolysaccharide (LPS)-induced septic shock in mice. For this purpose, mice or rats (n 10) were given the probiotic (5×108 colony-forming units/ml drinking water), starting 2 weeks before damage induction. A control group (n 10) without probiotic was also used for reference. Colitis was induced in rats by intracolonic administration of TNBS (10 mg) and after 1 week was evaluated both histologically and biochemically (myeloperoxidase activity, glutathione content, inducible NO synthase (iNOS) expression)(Reference Peran, Sierra and Comalada3). Septic shock was induced in mice by administering LPS (40 mg/kg, intraperitoneally) and the mice killed 24 h later, when colon and spleen were removed. Colonic iNOS expression was determined by Western blot, and activated T-cells were obtained from spleens by concanavalin A incubation and the immune response evaluated by RT–PCR or ELISA for different cytokines (IL-2, -5, -6 and -10). The results showed that L. salivarius was able to ameliorate both the local and systemic altered immune response. The probiotic exerted intestinal anti-inflammatory activity, since it significantly reduced the extension of the colonic damage induced by TNBS in comparison with non-treated colitic rats; this effect was accompanied by a 42% reduction in myeloperoxidase activity (P<0.05), a 44% increase in glutathione content (P<0.05) and a reduction in colonic iNOS. Moreover, the probiotic treatment significantly prevented the increase in colonic weight (mg/cm) induced by septic shock (264 (se 15) v. 322 (se 15); P<0.05), without showing differences from normal mice (246 (se 14)). Similarly, the LPS-induced colonic iNOS expression was lower in the probiotic-treated mice (30%). LPS also stimulated the expression of different cytokines assayed in the splenocytes, while the probiotic-treated mice showed a reduction in cytokine expression of 80% for IL-5 and 100% for both IL-2 and IL-6 (Figure 1). IL-10 secretion was reduced in control mice (603 (se 102) pg/ml; P<0.05) in comparison with the normal group (1064 (se 80) pg/ml), which was increased in probiotic-treated mice (1034 (se 150 pg/ml; P<0.05) when compared with the LPS control group. In conclusion, the immunomodulatory properties of the probiotic L. salivarius are not restricted to the intestine, since it is also able to ameliorate the alteration in the systemic immune response derived from LPS administration to mice.
Figure 1. Lactobacillus salivarius administration reduced cytokine expression (RT-PCR) in LPS-induced septic shock in mice.
