scholarly journals The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response

2020 ◽  
Vol 8 (1) ◽  
pp. e000930 ◽  
Author(s):  
Fernanda I Arnaldez ◽  
Steven J O'Day ◽  
Charles G Drake ◽  
Bernard A Fox ◽  
Bingqing Fu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Interleukin 6 ◽  
Severe Disease ◽  
Systemic Inflammatory Response ◽  
Interleukin 17 ◽  
Extensive Experience ◽  
Necrosis Factor Alpha ◽  
The Usa ◽  
Immunotherapy Of Cancer ◽  
Novel Coronavirus

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.

scholarly journals Toll-like receptor linked cytokine profiles in cerebrospinal fluid discriminate neurological infection from sterile inflammation

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Simone M Cuff ◽  
Joseph P Merola ◽  
Jason P Twohig ◽  
Matthias Eberl ◽  
William P Gray
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Practice ◽  
Inflammatory Response ◽  
Nosocomial Infection ◽  
Pathway Analysis ◽  
Interleukin 6 ◽  
Sterile Inflammation ◽  
Interleukin 17 ◽  
Toll Like Receptor ◽  
Fluid Biomarker

Abstract Rapid determination of an infective aetiology causing neurological inflammation in the cerebrospinal fluid can be challenging in clinical practice. Post-surgical nosocomial infection is difficult to diagnose accurately, as it occurs on a background of altered cerebrospinal fluid composition due to the underlying pathologies and surgical procedures involved. There is additional diagnostic difficulty after external ventricular drain or ventriculoperitoneal shunt surgery, as infection is often caused by pathogens growing as biofilms, which may fail to elicit a significant inflammatory response and are challenging to identify by microbiological culture. Despite much research effort, a single sensitive and specific cerebrospinal fluid biomarker has yet to be defined which reliably distinguishes infective from non-infective inflammation. As a result, many patients with suspected infection are treated empirically with broad-spectrum antibiotics in the absence of definitive diagnostic criteria. To begin to address these issues, we examined cerebrospinal fluid taken at the point of clinical equipoise to diagnose cerebrospinal fluid infection in 14 consecutive neurosurgical patients showing signs of inflammatory complications. Using the guidelines of the Infectious Diseases Society of America, six cases were subsequently characterized as infected and eight as sterile inflammation. Twenty-four contemporaneous patients with idiopathic intracranial hypertension or normal pressure hydrocephalus were included as non-inflamed controls. We measured 182 immune and neurological biomarkers in each sample and used pathway analysis to elucidate the biological underpinnings of any biomarker changes. Increased levels of the inflammatory cytokine interleukin-6 and interleukin-6-related mediators such as oncostatin M were excellent indicators of inflammation. However, interleukin-6 levels alone could not distinguish between bacterially infected and uninfected patients. Within the patient cohort with neurological inflammation, a pattern of raised interleukin-17, interleukin-12p40/p70 and interleukin-23 levels delineated nosocomial bacteriological infection from background neuroinflammation. Pathway analysis showed that the observed immune signatures could be explained through a common generic inflammatory response marked by interleukin-6 in both nosocomial and non-infectious inflammation, overlaid with a toll-like receptor-associated and bacterial peptidoglycan-triggered interleukin-17 pathway response that occurred exclusively during infection. This is the first demonstration of a pathway dependent cerebrospinal fluid biomarker differentiation distinguishing nosocomial infection from background neuroinflammation. It is especially relevant to the commonly encountered pathologies in clinical practice, such as subarachnoid haemorrhage and post-cranial neurosurgery. While requiring confirmation in a larger cohort, the current data indicate the potential utility of cerebrospinal fluid biomarker strategies to identify differential initiation of a common downstream interleukin-6 pathway to diagnose nosocomial infection in this challenging clinical cohort.

scholarly journals Procalcitonin and Interleukin-6 for predicting culturenegative and culture positive bacterial sepsis in critically ill patients with systemic inflammatory response syndrome

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Mohd Basri Mat Nor ◽  
Azrina Md Ralib
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Interleukin 6 ◽  
Systemic Inflammatory Response ◽  
Bacterial Sepsis ◽  
Saps Ii Score ◽  
Culture Positive ◽  
Culture Negative

Introduction: Differentiation between culture-negative bacterial sepsis (BS), culturepositive BS and non-infectious systemic inflammatory response syndrome (SIRS) among critically ill patients remains a diagnostic challenge to the intensive care unit (ICU) physicians. This study aimed to evaluate the role of procalcitonin (PCT) and interleukin-6 (IL-6) in predicting non-infectious SIRS, culture-negative BS and culture-positive BS in the ICU. Methods: This prospective observational study was conducted in a tertiary ICU in Pahang. The patients were divided into sepsis and non-infectious SIRS based on clinical assessment with or without positive cultures. Patients with positive cultures were further divided into bacteraemia and positive other culture. The PCT and IL-6 were measured daily over the first 3 days. Results: Two hundred and thirty nine consecutive patients diagnosed with SIRS were recruited, of whom 164 (69%) had sepsis. Among sepsis patients, there were 62 (37.8%) culture positive and 102 (62.2%) culture negative. Of these, 27 (16.5%) develop bacteraemia. The most common site of infection was respiratory (34.4%). Post-LSD analyses showed significant difference in the PCT between culture negative sepsis and SIRS (p=0.01); and positive other culture and SIRS (p=0.04).  On the other hand IL-6 cannot differentiate between SIRS and negative culture sepsis (p=0.06). Both PCT and IL-6 predicted bacteraemia with an AUC of 0.70 (0.57 to 0.82) and 0.68 (0.53 to 0.70). IL-6 is independently associated with bacteraemia and other culture after adjusting for age, sex, hypertension, SAPS II score and day 1 PCT. Conclusions: Procalcitonin but not Interleukin-6 is able to differentiate SIRS from culture-negative BS. However, IL-6 is independently associated with bacteraemia and other culture.

ELEVATED INTERLEUKIN–6 AND FERRITIN LEVELS EXACERBATE SEVERITY OF 2019 NOVEL CORONAVIRUS DISEASE (COVID-19): A PILOT STUDY

2021 ◽  
pp. 16-19
Author(s):  
Shelesh Kumar Swami ◽  
Nitesh Kumar Chauhan ◽  
Shuchi Goyal ◽  
A.K. Verma ◽  
Shweta Biyani
Keyword(s):  
Pilot Study ◽  
Interleukin 6 ◽  
Severe Disease ◽  
Close Monitoring ◽  
Medical Practitioners ◽  
Resultant Data ◽  
Initial Symptoms ◽  
Severe Group ◽  
Novel Coronavirus ◽  
Loss Of Appetite

Background & objectives: The 2019 novel coronavirus disease (COVID-19) pandemic is a big challenge for scientic and medical eld. Progression of severe disease is a difcult problem in treatment. Therefore, there is essential need to recognize severe forms of COVID-19 early in the disease course. Identication of effective biomarkers are able to classify patients based on severity. In this pilot study, we aimed to validate the association between immunologic biomarkers Interleukin-6 and ferritin with the severity of the COVID-19. Methods: A total of 1443 patients diagnosed with COVID-19 were enrolled including a severe group and a nonsevere group. Baseline clinical characteristics were collected. Serum interleukin-6 and ferritin were measured and the resultant data was statistically analyzed. Results: The most common initial symptoms were fever (68.81%) and cough (47.82%), followed by loss of appetite (9.28%), fatigue (17.46%) and breathlessness (15.52%). Level of IL-6 and Ferritin were signicantly higher in the severe patients (p<.05 for both) compared with nonsevere patients. Interpretation & conclusions: This pilot study conrmed that IL-6 and ferritin biomarkers are closely associated with the severity of COVID-19. Assessment of these biomarkers could be helpful to medical practitioners in starting treatment and close monitoring against COVID-19 infection which could improve prognosis and lower mortality

scholarly journals Systemic Inflammatory Response during Laparotomy

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Ahmad Mahamid ◽  
Basel Jabarin ◽  
Gidon Almogy
Keyword(s):  
Animal Models ◽  
Inflammatory Response ◽  
Inflammatory Mediators ◽  
Venous Blood ◽  
White Blood Cells ◽  
Systemic Inflammatory Response ◽  
Secondary Peritonitis ◽  
Necrosis Factor Alpha ◽  
Female Ratio ◽  
Generalized Peritonitis

Background. The aim of this study was to analyze the influence of laparotomy on the systemic inflammatory response in human patients suffering from secondary peritonitis.Study Design. A prospective study investigating the levels of white blood cells, C-reactive protein, platelets, interleukin-six, and tumor necrosis factor-alpha during laparotomy in five patients who suffered from secondary peritonitis. Six venous blood samples were collected perioperatively from each patient. The data were summarized by descriptive statistics and presented in a box plot. The hypothesis was that laparotomy increases the systemic inflammatory response, as has been described in animal models in previous studies.Results. The median age of the patients in this study was 84 years, the male to female ratio was 2 : 3, and the mortality rate was 80%. The most common cause of generalized peritonitis was ischemia of the colon. Analysis of the data showed no significant changes in the level of plasma inflammatory mediators during the surgical procedure, except for the platelet count which showed a significant decrease(P=0.001).Conclusions. In contrast to experience with animal models, laparotomy in human patients with secondary peritonitis did not significantly increase the systemic inflammatory response. Furthermore, it contributed in significantly decreasing some of the systemic inflammatory mediators.

Upregulation of Prostaglandin E2and Interleukins in the Central Nervous System and Peripheral Tissue during and after Surgery in Humans

2006 ◽  
Vol 104 (3) ◽  
pp. 403-410 ◽  
Author(s):  
Asokumar Buvanendran ◽  
Jeffrey S. Kroin ◽  
Richard A. Berger ◽  
Nadim J. Hallab ◽  
Chiranjeev Saha ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Prostaglandin E2 ◽  
Interleukin 6 ◽  
Hip Replacement ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Background The central and peripheral inflammatory response to surgery may influence patient outcomes. This study examines the time course and clinical relevance of changes in prostaglandin E2 and cytokines in cerebrospinal fluid, local tissue (surgical site), and circulating blood during and after total hip replacement. Methods Thirty osteoarthritis patients undergoing primary total hip arthroplasty with spinal anesthesia were randomly allocated to three groups (n = 10/group): placebo for 4 days before surgery and on the morning of surgery; placebo for 4 days before surgery and oral rofecoxib 50 mg on the morning of surgery; oral rofecoxib 50 mg for 4 days before surgery and the morning of surgery. Cerebrospinal fluid and plasma were collected before surgery and up to 30 h after incision for measurement of prostaglandin E2 and interleukins. When hip replacement was complete, a drain was placed in the hip wound and exudates were collected at 3 to 30 h after incision. Results Cerebrospinal fluid showed an initial increase in interleukin 6 and a later rise in prostaglandin E2 concentration after surgery; interleukin 1beta and tumor necrosis factor alpha were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E2, interleukin 6, interleukin 8, and interleukin 1beta; tumor necrosis factor alpha decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E2 was positively correlated with postoperative pain and cerebrospinal fluid interleukin 6 with sleep disturbance. Poorer functional recovery was positively correlated with increased surgical site prostaglandin E2. Conclusions These results suggest that upregulation of prostaglandin E2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.

Prognostic value of serum interleukin-6 and YKL-40 and systemic inflammatory response in patients with unresectable pancreatic cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 267-267
Author(s):  
Inna Chen ◽  
Christian Dehlendorff ◽  
Benny Vittrup Jensen ◽  
Per Pfeiffer ◽  
Jon K. Bjerregaard ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Inflammatory Response ◽  
Interleukin 6 ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
White Blood Cells ◽  
Multivariable Analysis ◽  
Laboratory Data ◽  
Cox Proportional Hazards ◽  
Systemic Inflammatory Response

267 Background: Interleukin-6 (IL-6) and YKL-40 (CHI3L1) are produced by pancreatic cancer (PC) cells and macrophages and activate inflammation. The aim of this prospective-retrospective biomarker study was to determine the prognostic value of serum IL-6 and YKL-40 and systemic inflammatory response in patients with PC receiving palliative chemotherapy. Methods: 625 patients with PC (M/F: 283/342; age <70 vs. ≥70: 395/230; ECOG PS of 0/1/2/3: 214/315/92/4; stage 3 vs. 4: 129/496; treated with gemcitabine n=437, FOLFIRINOX n=117, gemcitabine and nab-Paclitaxel n=54 or other n=17) were included in the BIOPAC biomarker study from 5 hospitals in Denmark. Pretreatment serum values of IL-6 (R&D Systems), YKL-40 (Quidel), and CA 19-9 (Siemens) were determined. Patients were grouped as low vs. high, dichotomized using cut-off for IL-6 > 4.92 pg/ml, for CA19-9 > 2183 U/ml and for YKL-40 > 95% age-corrected percentile. The main outcome was overall survival (OS) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were computed using Cox proportional hazards regression. Results: 598 (95.7%) patients died during follow-up. In univariate analysis elevated IL-6 (HR 1.93, 95% CI 1.63-2.28) and elevated YKL-40 (HR 1.74, 95% CI 1.47-2.05) were associated with short OS. Similar results were found if IL-6 and YKL-40 were included as continuous log2-transformed variables. Multivariable analysis showed that elevated IL-6 (HR 1.61, 95% CI 1.33-1.94), elevated YKL-40 (HR 1.36, 95% CI 1.13-1.64), elevated CA19-9 (HR 1.30, 95% CI 1.09-1.56), higher PS (1 vs. 0; HR 1.46, 95% CI 1.21-1.77 and PS 2 vs. 0; HR 2.73, 95% CI 2.08-3.58) and stage 4 vs. 3 (HR 1.79, 95% CI 1.44-2.24) were independently associated with a poor OS. In a subgroup of 386 patients with available laboratory data, higher C-reactive protein (HR 1.20, 95% CI 1.13-1.26), white blood cells (HR 1.41, 1.17-1.71) and absolute neutrophils count (HR 1.35, 95% CI 1.15-1.59) log2-transformed and adjusted for age, sex, PS, CA 19-9 and stage were associated with short OS. Conclusions: Serum IL-6, YKL-40 and CA19-9 along with CRP, WBC and ANC are independent prognostic biomarkers in patients with unresectable PC.

Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome

1999 ◽  
Vol 27 (7) ◽  
pp. 1262-1264 ◽  
Author(s):  
Takumi Taniguchi ◽  
Yuichi Koido ◽  
Jyunichi Aiboshi ◽  
Teruyo Yamashita ◽  
Shinichiro Suzaki ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Interleukin 6 ◽  
Interleukin 10 ◽  
Systemic Inflammatory Response ◽  
Poor Outcome

Interleukin 6 and interleukin 8 play important roles in systemic inflammatory response syndrome of meconium peritonitis

Surgery Today ◽  
2011 ◽  
Vol 42 (5) ◽  
pp. 431-434 ◽  
Author(s):  
Yutaka Kanamori ◽  
Kan Terawaki ◽  
Hajime Takayasu ◽  
Masahiko Sugiyama ◽  
Makoto Komura ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Interleukin 6 ◽  
Systemic Inflammatory Response ◽  
Interleukin 8 ◽  
Meconium Peritonitis
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