Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia

Millo, Julian; Schultz, Marcus J.; Williams, C. M.; Weverling, Gerrit Jan; Ringrose, T. J.; Mackinlay, C; Poll, Tom van der; Garrard, Christopher S.

doi:10.1007/s00134-003-2060-0

Cited by 55 publications

(42 citation statements)

References 18 publications

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“…The current authors chose to measure IL-6 and TNF-a because they play an important role in the activation of coagulation and attenuation of fibrinolysis, respectively, during sepsis [7]. However, in the present study, TNF-a levels in BALF were either not detectable or very low, and varied widely, as previously demonstrated in both developing VAP and established community-acquired pneumonia [10,11]. Likewise, concentrations of IL-6 showed a large variation.…”

Section: Discussionmentioning

confidence: 40%

Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection

Choi

Schultz

Till³

et al. 2004

European Respiratory Journal

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Severe infection is associated with profound alterations in the systemic haemostatic balance, with activation of coagulation and suppressed fibrinolysis. Within the alveolar compartment, similar disturbances have been described during pulmonary inflammation. The current authors investigated whether local haemostasis was influenced during ventilator-associated pneumonia (VAP).In five patients with unilateral VAP, bronchoalveolar lavage fluid (BALF) was obtained from both the infected site (as identified on chest radiograph) and the contralateral noninfected lung (with no clinical or radiographic abnormalities). Markers for coagulation and fibrinolysis were compared between infected and noninfected lungs. A total of 10 healthy volunteers and 10 mechanically ventilated patients without pneumonia served as controls.Strong activation of coagulation (high levels of thrombin-antithrombin complexes, soluble tissue factor and factor VIIa) was detected in BALF from infected lungs, compared with that from noninfected lungs and controls. Furthermore, in infected lungs, fibrinolysis was depressed, with high levels of plasminogen activator inhibitor type 1.In conclusion, ventilator-associated pneumonia is characterised by a hypercoagulant state at the site of infection. Eur Respir J 2004; 24: 786-789.

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Section: Discussionmentioning

confidence: 40%

Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection

Choi

Schultz

Till³

et al. 2004

European Respiratory Journal

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“…Sequential determinations showed a pattern of decline with progressive normalisation of all pro-and anti-inflammatory cytokines detected that was accompanied by clinical recovery. In the studies with a shorter observational period, that is those with only hourly determinations, no variations in cytokine levels were found [64,63], indicating that the kinetics of cytokine production takes days to produce detectable changes. Plasma levels remained elevated or were higher than on admission in some of the patients who died [61,67].…”

Section: Cytokines and Pneumonia: From Mice To Human Studiesmentioning

confidence: 89%

Of mice and men: innate immunity in pneumococcal pneumonia

Calbo

Garau

2010

International Journal of Antimicrobial Agents

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“…For the clinical management of individual patients with systemic inflammation, this means that temporal characteristics of both pro-and anti-inflammatory mediators must be taken into account for an accurate assessment of the inflammatory risk profile. Antiinflammatory effects are mediated by, e.g., IL-10, transforming growth factor (TGF)-β, IL-4, plasma IL-1 receptor antagonist (IL-1ra) and soluble TNF receptors (TNF-sr; Rivera-Chavez et al 2003;Millo et al 2004). During onpump cardiac surgery, increased IL-8 plasma levels were accompanied by elevated IL-10 levels at the end of CPB, followed by IL-1ra and TNF-sr peaks later on (McBride et al 1996).…”

Section: Systemic Inflammatory Responses After On-pump Cardiac Surgerymentioning

confidence: 98%

Hsp70 and cardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects

Jong

Schadenberg

Jansen

et al. 2009

Cell Stress and Chaperones

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Open heart surgery is a unique model to study the interplay between cellular injury, regulation of inflammatory responses and tissue repair. Stress-inducible heat shock protein 70-kDa (Hsp70) provides a molecular link between these events. In addition to molecular chaperoning, Hsp70 exerts modulatory effects on endothelial cells and leukocytes involved in inflammatory networks. Hsp70 residing in the intracellular compartment is part of an inhibitory feedback loop that acts on nuclear factor kappaB (NF-kappaB). In contrast, extracellular Hsp70 is recognized by multiple germline-encoded immune receptors, e.g., Toll-like receptor (TLR) 2, TLR4, LOX-1, CD91, CD94, CCR5 and CD40. Hsp70 is thereby able to enhance chemotaxis, phagocytosis and cytolytic activity of innate immune cells and stimulate antigen-specific responses. These apparent contradictory pro- and anti-inflammatory effects of endogenous Hsp70 in the context of cardiac surgery are still not fully understood. An all-embracing model of the compartmentalized effects of endogenous Hsp70 in the orchestration of inflammatory responses in cardiac surgery is proposed.

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Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia

Abstract: Our results suggest that the production of important cytokines and cytokine inhibitors is compartmentalised within the lung in critically ill mechanically ventilated patients who develop VAP.

Cited by 55 publications

References 18 publications

Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection

Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection

Of mice and men: innate immunity in pneumococcal pneumonia

Hsp70 and cardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects

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