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Zinc and Inflammation in Sepsis

NCT01328509 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 39

Last updated 2013-07-08

No results posted yet for this study

Summary

The purpose of the proposed project is to investigate measures of zinc status in relation to oxidative stress and inflammation in patients with sepsis. We hypothesise that zinc depletion can modulate inflammatory responses, leading to increased oxidative stress and mitochondrial dysfunction.

Sepsis is a severe infection is the leading cause of death in critically ill patients \[1\]. Zinc deficiency impairs overall immune function and resistance to infection \[2\]. In vitro exposure of monocytes to lipopolysaccharide (LPS) leads to decreased cellular zinc content \[3\] and zinc redistribution has been shown in human volunteers in response to LPS \[4\]. Zinc depletion occurs in hospitalized patients including those with infections, the elderly, alcoholics, trauma or burns \[5-8\], conditions which are common among critically ill patients with sepsis. In a mouse model of sepsis, zinc depletion prior to sepsis resulted in more inflammation and more severe organ injury and increased mortality \[9\]. In patients with sepsis, early feeding with zinc resulted in faster recovery of organ function compared with control \[10\]. Zinc status is likely to be compromised in the critically ill and that zinc depletion may affect inflammatory responses and recovery.

Although zinc is not an antioxidant itself, it binds to metallothionein \[11\] and zinc supplementation decreases oxidative stress \[12\]. Oxidative stress has been consistently reported in patients with sepsis \[13-15\]. We have recently shown that protection of mitochondrial function with antioxidants can reduce organ damage in rats \[16\]. Pentraxin-3 is an inflammatory marker which is regulated in part by antioxidants and plays a key role in innate immunity \[17\].

The consequences of zinc deficiency may relate, in part, to its effects on nuclear factor NFκB, a transcription factor crucial to the signalling networks involved in sepsis \[18\]. Higher NFκB activity is associated with increased mortality in patients with sepsis \[19,20\]. It is likely that compromised antioxidant defences and inflammation occurs as a consequence of zinc deficiency.

We propose to measure plasma zinc and metallothionein mRNA status in relation to inflammatory markers including key cytokines, pentraxin-3, markers of oxidative stress and antioxidant status in patients with sepsis.

Conditions

Sponsors & Collaborators

  • UK Intensive Care Society

    collaborator UNKNOWN

  • University of Aberdeen

    lead OTHER

Principal Investigators

  • Helen Galley, PhD · University of Aberdeen

  • Nigel Webster, PhD · University of Aberdeen

Eligibility

Min Age
16 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2012-01-31
Primary Completion
2013-05-31
Completion
2013-05-31

Countries

  • United Kingdom

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01328509 on ClinicalTrials.gov