Lactobacillus casei modulates the inflammation-coagulation interaction in a pneumococcal pneumonia experimental model

Cecilia Haro,Hortensia Zelaya,Susana Alvarez,Julio Villena,Graciela Agüero

doi:10.1186/1476-9255-6-28

Abstract

BackgroundWe have previously demonstrated that Lactobacillus casei CRL 431 administration improved the resistance to pneumococcal infection in a mouse model.MethodsThis study examined the effects of the oral administration of Lactobacillus casei CRL 431 (L. casei) on the activation of coagulation and fibrinolytic systems as well as their inhibitors during a Streptococcus pneumoniae infection in mice.ResultsThe alveolo-capillary membrane was damaged and the coagulation system was also activated by the infection. As a consequence, we could see fibrin(ogen) deposits in lung histological slices, increased levels of thrombin-antithrombin complex (TATc) in bronchoalveolar lavage (BAL) and plasma, decrease in prothrombin activity (PT) and prolonged activated partial thromboplastin time test (APTT) values. Factor VII (FVII) and factor X (FX) were decreased in plasma, whereas fibrinogen (F) and factor VIII (FVIII) were increased. The low levels of protein C (PC) in BAL and plasma proved damage on inhibitory activity. The infected animals showed reduced fibrinolytic activity, evidenced by an increase in plasminogen activation inhibitor-1 (PAI-1) in BAL and plasma. The pathogen induced an increase of TNF-α, IL-1β and IL-6 in BAL and serum a few hours after challenge followed by a significant decrease until the end of the assayed period. IL-4 and IL-10 in BAL and serum were also augmented, especially at the end of the experiment. The animals treated with L. casei showed an improvement of alveolo-capillary membrane, lower fibrin(ogen) deposits in lung and decrease in TATc. APTT test and PT, FVII and FX activity were normalized. L. casei group showed lower F levels than control during whole experiment. In the present study no effect of L. casei on the recovery of the inhibitory activity was detected. However, L. casei was effective in reducing PAI-1 levels in BAL and in increasing anti-inflammatory ILs concentration.ConclusionL. casei proved effective to regulate coagulation activation and fibrinolysis inhibition during infection, leading to a decrease in fibrin deposits in lung. This protective effect of L. casei would be mediated by the induction of higher levels of IL-4 and IL-10 which could regulate the anti-inflammatory, procoagulant and antifibrinolytic effects of TNF-α, IL-1β and IL-6.

Highlights

We have previously demonstrated that Lactobacillus casei CRL 431 administration improved the resistance to pneumococcal infection in a mouse model
L. casei proved effective to regulate coagulation activation and fibrinolysis inhibition during infection, leading to a decrease in fibrin deposits in lung. This protective effect of L. casei would be mediated by the induction of higher levels of IL-4 and IL-10 which could regulate the antiinflammatory, procoagulant and antifibrinolytic effects of tumor necrosis factor alpha (TNF-α), IL-1β and IL-6
Challenge with S. pneumoniae caused increases in bronchoalveolar lavage (BAL) albumin concentration and LDH activity in both groups, but these parameters were significantly lower in L. casei treated mice (Figure 1)

Summary

Introduction

We have previously demonstrated that Lactobacillus casei CRL 431 administration improved the resistance to pneumococcal infection in a mouse model. The hallmark of inflammatory lung diseases are fibrin deposits, which enhance the inflammatory responses by increasing vascular permeability, activating endothelial cells to produce proinflammatory mediators, and eliciting recruitment and activation of neutrophils [2]. Excessive fibrin deposition within the airways results from severe inflammation, with increased activation of coagulation, and may compromise pulmonary integrity and function [3,2]. Current evidence from human studies suggests that in lung injury there is augmented tissue factor expression, down regulation of protein C (PC), and higher plasminogen activator inhibitor -1 (PAI-1) levels. Together, these abnormalities shift the intra-alveolar environment from anticoagulant and profibrinolytic to procoagulant and antifibrinolytic [4]. An insufficiently controlled response can lead to a situation in which coagulation and thrombosis contribute to disease [1]

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Conclusion