Is Interleukin-6 a better predictor of successful antibiotic therapy than procalcitonin and C-reactive protein? A single center study in critically ill adults

Weidhase, Lorenz; Wellhöfer, Daniel; Schulze, Gero; Kaiser, Thorsten; Drogies, Tim; Wurst, Ulrike; Petros, Sirak

doi:10.1186/s12879-019-3800-2

Cited by 53 publications

(64 citation statements)

References 33 publications

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“…Measurement of the immune status, such as PD-1/programmed death ligand 1 (PD-L1) expression on T cells and dendritic cells, lymphocyte count, HLA-DR expression on monocytes, immunoglobulin levels and inflammatory markers (e.g. CRP, IL-6 or PCT) are potential diagnostic biomarkers to be considered [105,118,119]. Low HLA-DR expression, in particular, may correlate with low lymphocyte counts in the differential blood count and lymphocyte count is also readily available in most hospitals.…”

Section: Patients With Immunosuppression Clinical Phenotypementioning

confidence: 99%

Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis

Nierhaus

Berlot

Kindgen‐Milles

et al. 2020

Ann. Intensive Care

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Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite treatment being in line with current guidelines, mortality remains high in those with septic shock. Intravenous immunoglobulins represent a promising therapy to modulate both the pro- and anti-inflammatory processes and can contribute to the elimination of pathogens. In this context, there is evidence of the benefits of immunoglobulin M (IgM)- and immunoglobulin A (IgA)-enriched immunoglobulin therapy for sepsis. This manuscript aims to summarize current relevant data to provide expert opinions on best practice for the use of an IgM- and IgA-enriched immunoglobulin (Pentaglobin) in adult patients with sepsis. Main text Sepsis patients with hyperinflammation and patients with immunosuppression may benefit most from treatment with IgM- and IgA-enriched immunoglobulin (Pentaglobin). Patients with hyperinflammation present with phenotypes that manifest throughout the body, whilst the clinical characteristics of immunosuppression are less clear. Potential biomarkers for hyperinflammation include elevated procalcitonin, interleukin-6, endotoxin activity and C-reactive protein, although thresholds for these are not well-defined. Convenient biomarkers for identifying patients in a stage of immune-paralysis are still matter of debate, though human leukocyte antigen–antigen D related expression on monocytes, lymphocyte count and viral reactivation have been proposed. The timing of treatment is potentially more critical for treatment efficacy in patients with hyperinflammation compared with patients who are in an immunosuppressed stage. Due to the lack of evidence, definitive dosage recommendations for either population cannot be made, though we suggest that patients with hyperinflammation should receive an initial bolus at a rate of up to 0.6 mL (30 mg)/kg/h for 6 h followed by a continuous maintenance rate of 0.2 mL (10 mg)/kg/hour for ≥ 72 h (total dose ≥ 0.9 g/kg). For immunosuppressed patients, dosage is more conservative (0.2 mL [10 mg]/kg/h) for ≥ 72 h, without an initial bolus (total dose ≥ 0.72 g/kg). Conclusions Two distinct populations that may benefit most from Pentaglobin therapy are described in this review. However, further clinical evidence is required to strengthen support for the recommendations given here regarding timing, duration and dosage of treatment.

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Section: Patients With Immunosuppression Clinical Phenotypementioning

confidence: 99%

Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis

Nierhaus

Berlot

Kindgen‐Milles

et al. 2020

Ann. Intensive Care

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“…The blood IL-6 levels are elevated in patients with sepsis and septic shock [35,36], correlate with disease severity [35][36][37], and possibly predict unfavorable outcome [36]. Moreover, IL-6 could be a faster indicator of treatment success in adults with severe sepsis and septic shock compared to PCT and CRP [37]; however, some studies found no additive effect for IL-6 in the diagnosis of the severe infection in critically ill patients [38]. In a recently published systematic review regarding biomarkers of sepsis, Pierrakos et al indicated that IL-6 in comparison with PCT and/or CRP for sepsis diagnosis provided conflicting findings and that so far IL-6 was not evaluated for prognostic value in large clinical studies [39].…”

Section: Discussionmentioning

confidence: 99%

Utility of procalcitonin in a medical intensive care unit in Croatia

Brajković

Košuta

Tomek

et al. 2020

Wien Klin Wochenschr

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Aims To investigate the clinical benefit of routine procalcitonin (PCT) measurement in the medical intensive care unit (ICU) of a tertiary referral hospital. Methods Adult patients with suspected infections were included. White blood cells, C-reactive protein (CRP), and PCT were measured. Results In this study 129 patients of median age 64 years (interquartile range 39-89 years) were prospectively included. The Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were 21 ± 14 and 7 ± 6, respectively. Intensive care unit (ICU) mortality was 22.5%. Immunocompromised patients constituted 39.5%. A significant correlation was observed between PCT and APACHE II (Spearman's rho 0.461, p < 0.01), PCT and SOFA (Spearman's rho 0.494, p < 0.01) and PCT and CRP (Spearman's rho 0.403, p < 0.01). Most patients (n = 83, 64.3%) received antibiotics before admission. No difference in PCT (1.56 ± 8 µg/L vs. 1.44 ± 13 µg/L, p = 0.6) was observed with respect to previous antibiotic therapy. Levels of PCT and CRP were significantly increased in patients with positive blood cultures, the

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“…Finally, as IL‐6 and sIL‐6Rα are acute reactants, their plasma levels in non‐disease states are very low, but they increase rapidly and substantially in conditions of acute inflammation, such as myocardial infarction (MI), severe infections, and trauma . MI and trauma induce endothelial injury and the exposure of the subendothelial matrix at the site of vascular injury.…”

Section: Discussionmentioning

confidence: 99%

Physical proximity and functional cooperation of glycoprotein 130 and glycoprotein VI in platelet membrane lipid rafts

Houck

Yuan

Tian

et al. 2019

Journal of Thrombosis and Haemostasis

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Objective:Clinical and laboratory studies have demonstrated that platelets become hyperactive and prothrombotic in conditions of inflammation. We have previously shown that the proinflammatory cytokine interleukin (IL)-6 forms a complex with soluble IL-6 receptor α (sIL-6Rα) to prime platelets for activation by subthreshold concentrations of collagen. Upon being stimulated with collagen, the transcription factor signal transducer and activator of transcription (STAT) 3 in platelets is phosphorylated and dimerized to act as a protein scaffold to facilitate the catalytic action between the kinase Syk and the substrate phospholipase Cγ2 (PLCγ2) in collagen-induced signaling. However, it remains unknown how collagen induces phosphorylation and dimerization of STAT3. Methods and results:We conducted complementary in vitro experiments to show that the IL-6 receptor subunit glycoprotein 130 (GP130) was in physical proximity to the collagen receptor glycoprotein VI (GPVI in membrane lipid rafts of platelets.This proximity allows collagen to induce STAT3 activation and dimerization, and the IL-6-sIL-6Rα complex to activate the kinase Syk and the substrate PLCγ2 in the GPVI signal pathway, resulting in an enhanced platelet response to collagen. Disrupting lipid rafts or blocking GP130-Janus tyrosine kinase (JAK)-STAT3 signaling abolished the cross-activation and reduced platelet reactivity to collagen.Conclusion: These results demonstrate cross-talk between collagen and IL-6 signal pathways. This cross-talk could potentially provide a novel mechanism for inflammation-induced platelet hyperactivity, so the IL-6-GP130-JAK-STAT3 pathway has been identified as a potential target to block this hyperactivity. K E Y W O R D Scytokine receptor GP130, membrane microdomain, platelet activation, platelet membrane glycoproteins, STAT3 transcription factor | 1501 HOUCK et al.

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Is Interleukin-6 a better predictor of successful antibiotic therapy than procalcitonin and C-reactive protein? A single center study in critically ill adults

Cited by 53 publications

References 33 publications

Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis

Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis

Utility of procalcitonin in a medical intensive care unit in Croatia

Physical proximity and functional cooperation of glycoprotein 130 and glycoprotein VI in platelet membrane lipid rafts

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