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Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection
Örebro University, School of Medical Sciences. Department of Infectious Diseases.
Örebro University, School of Medical Sciences. Department of Infectious Diseases.
School of Medical Sciences, Örebro University, Örebro, Sweden. (Clinical Epidemiology and Biostatistics)
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
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2019 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 8, p. 1425-1434Article in journal (Refereed) Published
Abstract [en]

The severity of bloodstream infections (BSI) depends on pathogen, source, and host factors. Secretory leukocyte protease inhibitor (SLPI) counteracts tissue damage, balances inflammation, and is increased in pneumonia and sepsis. We aimed to evaluate whether SLPI production differs depending on etiology, disease severity, and sex in BSI and to correlate SLPI with markers of inflammation and immunosuppression. Of the adult patients with BSI, 109 were included and sampled repeatedly, from hospital admission through day 28. Controls (blood donors) were sampled twice. SLPI in plasma was measured with enzyme-linked immunosorbent assay (ELISA) technique. Streptococcus pneumoniae and Staphylococcus aureus etiology were associated with higher SLPI than Escherichia coli on days 1-2 and 3. On day 1-2, subjects with sepsis had higher SLPI concentrations than those with non-septic BSI. Pneumonia was associated with higher SLPI than a non-pulmonary source of infection. SLPI co-varied with inflammatory markers. SLPI concentrations did not differ with regard to sex in the full cohort, but men with pneumonia had higher SLPI than women on day 1-2. S. pneumoniae and S. aureus BSI were associated with higher SLPI, when compared to E. coli. Severity and pneumonia, as well as male sex in the pneumonia sub-cohort, were factors independently associated with higher SLPI.

Place, publisher, year, edition, pages
Springer, 2019. Vol. 38, no 8, p. 1425-1434
Keywords [en]
Bloodstream infection, SLPI, Secretory leukocyte protease inhibitor, Sepsis, Sepsis immunology
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:oru:diva-74324DOI: 10.1007/s10096-019-03567-2ISI: 000476492200005PubMedID: 31089838Scopus ID: 2-s2.0-85065985128OAI: oai:DiVA.org:oru-74324DiVA, id: diva2:1316684
Funder
Stiftelsen Olle Engkvist Byggmästare
Note

Funding Agencies:

Research Committee of Region Örebro County

Nyckelfonden Region Orebro County

Signe and Olof Wallenius trust

ALF project funding

Available from: 2019-05-20 Created: 2019-05-20 Last updated: 2020-05-04Bibliographically approved
In thesis
1. SLPI and soluble BTLA as immunological markers in severe bacterial infections
Open this publication in new window or tab >>SLPI and soluble BTLA as immunological markers in severe bacterial infections
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Clinical presentation, and outcome of infections are affected by host-, and etiology- (focus of infection and pathogen) related factors. The immune response is controlled by a network of regulating pathways.

This thesis focuses on Secretory Leukocyte Protease Inhibitor (SLPI), a protease inhibitor with anti-inflammatory properties, and the previously non-studied soluble isoform of B and T lymphocyte attenuator (sBTLA), a membrane-associated regulatory protein. Plasma concentrations of SLPI and sBTLA were assessed in relation to etiology, severity, mortality, and markers of inflammation and immunosuppression, in i) community-acquired pneumonia (CAP) (SLPI), ii) intensive care unit (ICU) treated severe sepsis and septic shock (sBTLA), and iii) dynamically in BSI (SLPI and sBTLA).

Main findings were: higher expression of SLPI in pneumonia, compared to other sources, higher initial concentrations in Streptococcus pneumoniae, and Staphylococcus aureus BSI, compared to Escherichia coli BSI, and higher SLPI concentrations in sepsis compared to non-septic BSI. Interestingly, men with pneumonia had higher plasma levels of SLPI, both in CAP and BSI. Likewise, sBTLA was associated with severity, but preferentially at higher organ failure scores. High sBTLA was associated with increased risk of early death (28 days) in ICU-treated septic patients, and with mortality at 90 days and one year in BSI. In particular, failure to normalize sBTLA on day 7, was indicative of worse long-term outcome. SLPI was associated with decreased monocytic HLA-DR expression, and sBTLA with decreased lymphocyte count, which might indicate a connection to sepsis-associated immunosuppression.

In conclusion, SLPI and sBTLA show association with severity, and markers of immune dysfunction, in sepsis and BSI. SLPI differs depending on etiology, while sBTLA may have prognostic implications. Our results propose that the pathobiological role of sBTLA, and the possible utility of SLPI and sBTLA in sepsis immune-profiling, should be further addressed in future studies.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 82
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 211
Keywords
SLPI, sBTLA, sepsis, bloodstream infection, pneumonia
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-80161 (URN)978-91-7529-335-6 (ISBN)
Public defence
2020-05-29, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2020-02-24 Created: 2020-02-24 Last updated: 2020-05-13Bibliographically approved

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Lange, AnnaCajander, SaraHultgren, Olof

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