Immunobiotics and inflammation-coagulation

Abstract

Probiotic lactic acid bacteria (LAB) strains can exert their beneficial effect on the host through their immunomudulatory activity and their anti-inflammatory properties. Although most research concerning the effect of probiotic lactobacilli on immune protection is focused on gastrointestinal tract pathogens, recent studies have centred on whether immunobiotics might sufficiently stimulate the common mucosal immune system to provide protection to other mucosal sites as well. On the other hand, increasing evidence points to an extensive cross-talk between inflammation and coagulation systems, whereby inflammation not only leads to activation of coagulation but coagulation also considerably affects inflammatory activity. In this chapter we focused on (i) the coagulation pathway, (ii) coagulation-inflammation interactions and specific coagulation abnormalities related to malnutrition and acute lung injury, and (iii) novel applications of immunobiotics in the inflammation-coagulation relationship. More specifically, in this chapter we reviewed the work of our laboratory on the use of immunobiotics to modulate the above relationship in immunocompetent and immunodeficient hosts. In our research, we demonstrated for the first time that a probiotic Lactobacillus casei CRL431 effectively regulated coagulation activation and fibrinolysis inhibition during respiratory infections, which led to a decrease in fibrin deposits in the lung of immunocompetent and immunocompromised mice. This protective effect of L. casei CRL431 was mediated by the induction of high levels of anti-inflammatory interleukins such as IL-4 and IL-10. These interleukins would contribute to regulate the pro-inflammatory, procoagulant and antifibrinolytic effects of TNF-alfa, IL-1 and IL-6 that were increased after the respiratory challenge. These findings can be useful to develop novel strategies using immunobiotics to reduce the damaging effects of clotting and enhance its beneficial contribution to immune reactions. Diseases associated with high levels of PAI-1 such as cardiovascular disease, acute lung injury and acute respiratory distress syndrome could be targets of these novel therapeutic strategies. In addition, it is to be hoped that the knowledge gained in the unraveling of the coagulation and inflammation pathophysiology will result in further refinements and improved therapies for patients with severe systemic injuries and septic shock. However, much remains to be learnt about the cellular and molecular mechanisms involved in the interaction between mucosal immune system, inflammation, coagulation and immunobiotic LAB.