Protective capacity of a IgM/IgA-enriched polyclonal immunoglobulin-G preparation in endotoxemia

Oesser, Steffen; Schulze, C.; Seifert, J.

doi:10.1007/s004330050115

Cited by 17 publications

(12 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The effects of IgM-IVIg on the EA levels following endotoxin application are mostly described for animal models when endotoxin and IgM-IVIg were administered in close succession and with short observational periods [ 7 , 21 , 22 ]. Most previous studies in humans focused on neonates and preterm infants, who differ in their immune responses from adults, or on neutropenic patients [ 8 , 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…The human polyspecific immunoglobulin preparation, Pentaglobin ® , is enriched in immunoglobulin class M (IgM) and thus seems capable of neutralizing bacterial endotoxins. This effect has been demonstrated in ex vivo experiments and a randomized controlled clinical trial [ 6 , 7 ]. Though the effects of IgM-enriched immunoglobulins (IgM-IVIg) on endotoxin levels in patients with sepsis have been investigated using the Limulus Amebocyte Lysis test (LAL) [ 8 ].…”

Section: Introductionmentioning

confidence: 94%

See 1 more Smart Citation

IgM-Enriched Immunoglobulin Attenuates Systemic Endotoxin Activity in Early Severe Sepsis: A Before-After Cohort Study

et al. 2016

View full text Add to dashboard Cite

IntroductionSepsis remains associated with a high mortality rate. Endotoxin has been shown to influence viscoelastic coagulation parameters, thus suggesting a link between endotoxin levels and the altered coagulation phenotype in septic patients. This study evaluated the effects of systemic polyspecific IgM-enriched immunoglobulin (IgM-IVIg) (Pentaglobin® [Biotest, Dreieich, Germany]) on endotoxin activity (EA), inflammatory markers, viscoelastic and conventional coagulation parameters.MethodsPatients with severe sepsis were identified by daily screening in a tertiary, academic, surgical ICU. After the inclusion of 15 patients, the application of IgM-IVIg (5 mg/kg/d over three days) was integrated into the unit’s standard operation procedure (SOP) to treat patients with severe sepsis, thereby generating “control” and “IgM-IVIg” groups. EA assays, thrombelastometry (ROTEM®) and impedance aggregometry (Multiplate®) were performed on whole blood. Furthermore, routine laboratory parameters were determined according to unit’s standards.ResultsData from 26 patients were included. On day 1, EA was significantly decreased in the IgM-IVIg group following 6 and 12 hours of treatment (0.51 ±0.06 vs. 0.26 ±0.07, p<0.05 and 0.51 ±0.06 vs. 0.25 ±0.04, p<0.05) and differed significantly compared with the control group following 6 hours of treatment (0.26 ±0.07 vs. 0.43 ±0.07, p<0.05). The platelet count was significantly higher in the IgM-IVIg group following four days of IgM-IVIg treatment (200/nl ±43 vs. 87/nl ±20, p<0.05). The fibrinogen concentration was significantly lower in the control group on day 2 (311 mg/dl ±37 vs. 475 mg/dl ±47 (p = 0.015)) and day 4 (307 mg/dl ±35 vs. 420 mg/dl ±16 (p = 0.017)). No differences in thrombelastometric or aggregometric measurements, or inflammatory markers (interleukin-6 (IL-6), leukocyte, lipopolysaccharide binding protein (LBP)) were observed.ConclusionTreatment with IgM-enriched immunoglobulin attenuates the EA levels in patients with severe sepsis and might have an effect on septic thrombocytopenia and fibrinogen depletion. Viscoelastic, aggregometric or inflammatory parameters were not influenced.Trial Registrationclinicaltrials.gov NCT02444871

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

IgM-Enriched Immunoglobulin Attenuates Systemic Endotoxin Activity in Early Severe Sepsis: A Before-After Cohort Study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Several properties of IgM-enriched intravenous immunoglobulins make this preparation suitable for immunomodulatory treatment in septic patients: it is able to facilitate the removal of apoptotic cells [50] and protect from endotoxin-related endothelial damage in parallel with successful antibiotic treatment [51]. Although there are no large prospective randomised trials to support their use on an evidence-based level, owing to the firm pathophysiological rationale it has been used for decades.…”

Section: When To Commence Adjuvant Therapies?mentioning

confidence: 99%

Can procalcitonin levels indicate the need for adjunctive therapies in sepsis?

Becze¹,

Molnár

Fazakas

2015

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

a b s t r a c tAfter decades of extensive experimental and clinical research, septic shock and the related multiple organ dysfunction still remain the leading cause of mortality in intensive care units (ICUs) worldwide. Defining sepsis is a difficult task, but what is even more challenging is differentiating infection-induced from non-infection-induced systemic inflammatory response-related multiple organ dysfunction. As conventional signs of infection are often unreliable in intensive care, biomarkers are used, of which one of the most frequently investigated is procalcitonin. Early stabilisation of vital functions via adequate supportive therapy and antibiotic treatment has resulted in substantial improvements in outcome over the last decades. However, there are certain patients who may need extra help, hence modulation of the immune system and the host's response may also be an important therapeutic approach in these situations. Polyclonal intravenous immunoglobulins have been used in critical care for decades. A relatively new potential approach could be attenuation of the overwhelming cytokine storm by specific cytokine adsorbents. Both interventions have been applied in daily practice on a large scale, with firm pathophysiological rationale but weak evidence supported by clinical trials. The purpose of this review is to give an overview on the pathophysiology of sepsis as well as the role and interpretation of biomarkers and their potential use in assisting adjunctive therapies in sepsis in the future.

show abstract

“…In animal experiments following administration of IVIGAM endotoxemia was induced by intraperitoneal inoculation of a sublethal dose of Escherichia coli and subsequent intravenous administration of an antimicrobial agent (27). Prophylactic administration of IVIGAM was found to significantly attenuate the antibiotic-induced increase in endotoxin activity as compared to the albumin control group.…”

Section: Immunoglobulins In Neonatesmentioning

confidence: 99%