Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection

Lange, A.; Cajander, Sara; Magnuson, Anders; Sundén-Cullberg, Jonas; Strålin, Kristoffer; Hultgren, Olof

doi:10.1007/s10096-019-03567-2

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…Our scRNAseq analyses also revealed the induction of SLPI, an anti-inflammatory molecule; IL-1R2, an antagonist of IL-1 signaling. Both of SLPI and IL-1R2 were shown to be elevated in septic monocytes collected from human patients (57,58). Collectively, the elevation of immunosuppressors such as PD-L1, SLPI and IL-1R2 and reduction of co-stimulatory molecules such as CD86 contribute to the immuno-suppressive phenotype characteristics of exhausted monocytes observed in clinical sepsis patients (11,31,57,58).…”

Section: Discussionmentioning

confidence: 99%

Development of Exhausted Memory Monocytes and Underlying Mechanisms

Pradhan

Geng

et al. 2021

Front. Immunol.

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Pathogenic inflammation and immuno-suppression are cardinal features of exhausted monocytes increasingly recognized in septic patients and murine models of sepsis. However, underlying mechanisms responsible for the generation of exhausted monocytes have not been addressed. In this report, we examined the generation of exhausted primary murine monocytes through prolonged and repetitive challenges with high dose bacterial endotoxin lipopolysaccharide (LPS). We demonstrated that repetitive LPS challenges skew monocytes into the classically exhausted Ly6Chi population, and deplete the homeostatic non-classical Ly6Clo population, reminiscent of monocyte exhaustion in septic patients. scRNAseq analyses confirmed the expansion of Ly6Chi monocyte cluster, with elevation of pathogenic inflammatory genes previously observed in human septic patients. Furthermore, we identified CD38 as an inflammatory mediator of exhausted monocytes, associated with a drastic depletion of cellular NAD+; elevation of ROS; and compromise of mitochondria respiration, representative of septic monocytes. Mechanistically, we revealed that STAT1 is robustly elevated and sustained in LPS-exhausted monocytes, dependent upon the TRAM adaptor of the TLR4 pathway. TRAM deficient monocytes are largely resistant to LPS-mediated exhaustion, and retain the non-classical homeostatic features. Together, our current study addresses an important yet less-examined area of monocyte exhaustion, by providing phenotypic and mechanistic insights regarding the generation of exhausted monocytes.

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Section: Discussionmentioning

confidence: 99%

Development of Exhausted Memory Monocytes and Underlying Mechanisms

Pradhan

Geng

et al. 2021

Front. Immunol.

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“…In peripheral circulation, the mean SLPI concentration showed a significant ( p < .05) increase in the P‐sepsis+ group as compared to the P‐sepsis− group and increased concentration of SLPI in the P‐sepsis+ bitch may be indicative of sepsis associated organ dysfunction. SLPI is known for its diverse immunological functions and to counteract the ill effects of tissue damage and inflammation in sepsis (Lange et al, 2019). The SLPI concentrations using a positive correlation of IL8 and SLPI expressions (data not shown) in the P‐sepsis+ bitch endometrium suggest the role of pro‐inflammatory cytokines in the regulation of SLPI production (VanWetering et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Serum concentrations of secretory leukocyte protease inhibitor and IL6 can predict the onset of sepsis in pyometra bitches

Sasidharan

Patra

et al. 2023

Reprod Domestic Animals

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As onset of sepsis adversely affects the prognosis of canine pyometra, finding biomarkers that would distinguish sepsis status would be useful in the clinical management. Accordingly, we hypothesized that differential expression of endometrial transcripts and circulating concentration of certain inflammatory mediators would discriminate pyometra‐led sepsis (P‐sepsis+) from those of pyometra without sepsis (P‐sepsis−). Bitches with pyometra (n = 52) were classified into P‐sepsis+ (n = 28) and P‐sepsis− (n = 24) based on vital clinical score and total leukocyte count. A group of non‐pyometra bitches (n = 12) served as control. The relative fold changes in the transcripts of IL6, IL8, TNFα, IL10, PTGS2, mPGES1 and PGFS, SLPI, S100A8, S100A12 and eNOS were determined by quantitative polymerase chain reaction. Furthermore, the serum concentrations of IL6, IL8, IL10, SLPI and prostaglandin F2α metabolite (PGFM) were assayed by ELISA. The relative fold changes in S100A12 and SLPI and mean concentrations of IL6 and SLPI were significantly (p < .05) higher in P‐sepsis+ than that of P‐sepsis− group. Receiver operating characteristic analysis revealed that serum IL6 had a diagnostic sensitivity of 78.6% and a positive likelihood ratio (LR+) of 2.09, at a cut‐off value of 15.7 pg/mL to diagnose P‐sepsis+ cases. Similarly, serum SLPI had a sensitivity of 84.6% and an LR+ of 2.23, at a cut‐off value of 2.0 pg/mL. It was concluded that SLPI and IL6 would serve as putative biomarkers for pyometra‐led sepsis in bitches. Monitoring SLPI and IL6 would be a useful adjunct to the established haemato‐biochemical parameters in customizing the treatment strategies and arriving at the decision for management of pyometra bitches with critical illness.

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“…Одним із протеїнів вродженого імунного захисту в респіраторних секретах є секреторний інгібітор протеази лейкоцитів (SLPI), який експресується макрофагами, нейтрофілами та епітелієм слизових оболонок [5]. Поси-лений синтез SLPI індукується інфекційними антигенами при патологічному процесі [5]. SLPI може бути одним із маркерів прогнозування стану гепатобіліарної системи при пневмонії у дітей раннього віку.…”

Section: вступunclassified

Possibilities of predicting lesions of the hepatobiliary system in children with community-acquired pneumonia

Dudnyk¹,

Khromykh²,

Pasik³

2021

Rep. of Vinnytsia Nation. Med. Univ.

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Annotation. The prognostic criteria of complications of community-acquired pneumonia and the possibility of developing disorders of the hepatobiliary system (HBS) depending on the concentration in the serum of the secretory leukocyte protease inhibitor (SLPI) were studied. The data of clinical and laboratory examination of 338 children with community-acquired pneumonia aged from one to three years were analyzed. Statistical processing of the results was performed using the system “IBM SPSS Statistica” 12 using parametric and non-parametric methods. It was found that in young children with pneumonia in the serum increases the concentration of SLPI, the level of which depends on the course and severity of pneumonia. It has been shown that the development of lobar pneumonia is significantly higher in patients from the SLPI cohort IV quartile (OR – 1.986, 95% CI – 1.864-2.356), compared with children from the cohort SLPI II and III quartile (OR – 0.476, 95% CI – 0.405- 0.559, OR – 0.494, 95% CI – 10.423-0.576, respectively). At the same time, at the values of SLPI at the level of III-IV quartile (OR – 1.923, 95% CI – 1.457-1.866) there is the development of community-acquired pneumonia. It was found that the development of pathological processes in the organs of HBS is associated with increased levels of SLPI. Thus, patients with polysegmental pneumonia and SLPI III/IV quartile (OR – 2.190, 95% CI – 1.810-2,754) are twice as likely to develop pathology of the hepatobiliary system than children with SLPI I/II quartile (OR – 1.153, 95% CI – 1.071-1.527). The established fact indicates the involvement of SLPI in the pathogenesis not only of pneumonia, but also in disorders of HBS.

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Plasma concentrations of secretory leukocyte protease inhibitor (SLPI) differ depending on etiology and severity in community-onset bloodstream infection

Cited by 5 publications

References 49 publications

Development of Exhausted Memory Monocytes and Underlying Mechanisms

Development of Exhausted Memory Monocytes and Underlying Mechanisms

Serum concentrations of secretory leukocyte protease inhibitor and IL6 can predict the onset of sepsis in pyometra bitches

Possibilities of predicting lesions of the hepatobiliary system in children with community-acquired pneumonia

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