Contribution of tumor necrosis factor-alpha to pulmonary cytokine expression and lung injury after hemorrhage and resuscitation

Abraham, Edward; Jesmok, Gary; Tuder, Rubin M.; Allbee, Janet; Chang, Yi‐Han

doi:10.1097/00003246-199508000-00004

Cited by 48 publications

(24 citation statements)

References 20 publications

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“…This priming insult leads to the induction of an extensive impairment on cellular immune responses and initial cytokine downregulation [11,12], affecting lung innate immunity [13]. These initial immunological events sensitize the host against the subsequent infectious insult as it is confirmed by Cue et al [14], who state that the hemorrhagic shock is a major determinant of the risk of infection and respiratory immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

Chronic Porcine Two-Hit Model with Hemorrhagic Shock and <i>Pseudomonas aeruginosa</i> Sepsis

et al. 2002

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Background: Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as ‘first hit’ followed by a Pseudomonas aeruginosa infusion as ‘second hit’. Materials and Methods: Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic shock with a 50% reduction of the mean arterial pressure and/or cardiac index for 45 min, followed by resuscitation, while the control group (n = 6) received no pretreatment. All chronically catheterized conscious pigs were challenged with a P. aeruginosa infusion (1.6 × 10⁷ CFU/kg/h for the first 24 h followed by 1.6 × 10⁶ CFU/kg/h for the next 24 h) and observed for another 48 h. Results: The two-hit group showed the following significant differences to the control group: higher APACHE II scores prior to sepsis induction, increased persisting mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) during bacterial challenge. In contrast, systemic vascular resistance (SVRI) was reduced at the end of the study. Throughout the observation period, the mean arterial pressure (MAP) was significantly reduced. Conclusions: The present study shows that the clinical course and hemodynamic effects of a P. aeruginosa sepsis will be aggravated by a preceding hemorrhagic shock during an oberservation period of 96 h. This two-hit model represents a valid, clinically relevant experimental protocol in sepsis research.

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Section: Discussionmentioning

confidence: 99%

Chronic Porcine Two-Hit Model with Hemorrhagic Shock and <i>Pseudomonas aeruginosa</i> Sepsis

et al. 2002

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“…In the setting of T/HS and TBI, initial efforts to understand the role of cytokines focused on post-traumatic blood levels and pharmacological therapy aimed at enhancing the protective cytokines and inhibiting the damaging cytokines are underway and have shown some improved survival rates in experimental animals [36]. Conclusions from these studies were that, at low concentrations, cytokines are important to the host response to trauma whereas in higher concentrations they are deleterious [37]. The best characterized and, apparently, earliest and most fundamental cytokine in the trauma-induced proinflammatory cascade is TNF-α.…”

Section: Human Studies Of T/hsmentioning

confidence: 99%

The Acute Inflammatory Response in Trauma /Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Namas¹,

Ghuma²,

Hermus

et al. 2008

Libyan Journal of Medicine

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Abstract; Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP's). DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future.

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“…Their synthesis and release is part of a complicated interaction towards the elimination of penetrating micro-organisms and tissue repair. In experimental studies pro-inflammatory cytokines infused in low concentrations are important to the host response to trauma [9]. In higher concentrations, however, they are deleterious, and to avoid auto-destructive effects of immune competent cells, pro-inflammatory cytokines are balanced by the production of anti-inflammatory cytokines [10,11].…”

Section: Introductionmentioning

confidence: 99%

Immune depression in musculoskeletal trauma

Reikerås

2010

Inflamm. Res.

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The immune responses after musculoskeletal trauma are physiological reactions of the organism to restore homeostasis. An imbalance between the early systemic inflammatory response syndrome and the later compensatory anti-inflammatory response syndrome may be responsible for organ dysfunction and increased susceptibility to infections. Cytokines are known to be integral components of the immune response, and the balance or imbalance of the different cytokines partly controls the clinical course in the patients. The major pro-inflammatory cytokines include tumor necrosis factor-alpha (TNF-a), interleukin-1beta (IL-1b), IL-6, and IL-8. These cytokines are predominantly produced by monocytes and macrophages, they mediate overlapping effects, and their actions can be additive. TNF-a and IL-1b are early regulators of the immune response, and both induce the release of secondary pro-inflammatory cytokines. IL-10 is an anti-inflammatory cytokine which reduces the synthesis of pro-inflammatory mediators. The extent of traumatic damage correlates with the immunological changes and determines a graded depression of leucocytes to express cytokines on edotoxin exposure. Correspondingly, it has become clinically evident that in unstable traumatised patients, the recommendation today is damage control orthopaedics, i.e. initial stabilisation of long bone fractures by external fixation followed by definitive stabilisation at about 1 week.

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Contribution of tumor necrosis factor-alpha to pulmonary cytokine expression and lung injury after hemorrhage and resuscitation

Abstract: These results indicate that TNF-alpha has an important role in the development of acute inflammatory lung injury after blood loss. Blockade of TNF-alpha with monoclonal antibodies significantly reduces hemorrhage-induced lung injury.

Cited by 48 publications

References 20 publications

Chronic Porcine Two-Hit Model with Hemorrhagic Shock and <i>Pseudomonas aeruginosa</i> Sepsis

Chronic Porcine Two-Hit Model with Hemorrhagic Shock and <i>Pseudomonas aeruginosa</i> Sepsis

The Acute Inflammatory Response in Trauma /Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Immune depression in musculoskeletal trauma

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