Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis

1997 ◽  
Vol 272 (2) ◽  
pp. R621-R630 ◽  
Author(s):  
W. Kozak ◽  
V. Poli ◽  
D. Soszynski ◽  
C. A. Conn ◽  
L. R. Leon ◽  
...  

Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fever, and lethargy) induced by infections bacterial and viral origin) and sterile tissue necrosis (burns and surgical traumas). Mice deficient in IL-6 (IL-6 KO) were generated by gene targeting. Homozygous IL-6 KO male and female mice and their appropriate controls were implanted with biotelemeters to monitor body temperature (Tb) and motor activity (Act). Normal circadian rhythms in Tb and Act as well as rates of food intake and weight gain did not differ significantly between sex-matched IL-6 KO and control groups at 30 degrees C in a 12:12-h light-dark cycle. Sterile tissue damage was induced in mice by subcutaneous injection of turpentine (0.1 ml, left hindlimb). Influenza pneumonitis was induced by intranasal inoculation of mouse-adapted influenza A virus (17.5 plaque-forming units). Lack of IL-6 completely prevented fever, anorexia, and cachexia because of turpentine abscess in both sexes. It did not prevent lethargy, although IL-6 KO mice recovered to normal Act significantly sooner than wild-type mice. Symptoms of sickness were only slightly modified during influenza virus infection in IL-6 KO mice. Attenuation of sickness behavior was more pronounced in IL-6 KO female than in male mice. We conclude that, although IL-6 is induced during both turpentine abscess and influenza infection, this cytokine appears to be more critical in induction of the symptoms of sickness behavior during sterile tissue abscess than during influenza infection.

2020 ◽  
Author(s):  
Ronghe Zhu ◽  
Cuie Chen ◽  
Qiu Wang ◽  
Xixi Zhang ◽  
Chaosheng Lu ◽  
...  

Abstract Purpose Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection.Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.


2016 ◽  
Vol 23 (6) ◽  
pp. 470-482 ◽  
Author(s):  
Carine K. Souza ◽  
Daniela S. Rajão ◽  
Crystal L. Loving ◽  
Phillip C. Gauger ◽  
Daniel R. Pérez ◽  
...  

ABSTRACTWhole inactivated virus (WIV) vaccines are widely used in the swine industry to reduce clinical disease against homologous influenza A virus (IAV) infection. In pigs experimentally challenged with antigenically distinct heterologous IAV of the same hemagglutinin subtype, WIV vaccinates have been shown to develop vaccine-associated enhanced respiratory disease (VAERD). We evaluated the impact of vaccine valency, age at vaccination, and duration between vaccination and challenge on the development of VAERD using vaccine containing δ1-H1N2 and challenge with pandemic H1N1 (pH1N1) virus. Pigs were vaccinated with monovalent WIV MN08 (δ1-H1N2) and bivalent (δ1-H1N2–H3N2 or δ1-H1N2–pH1N1) vaccines and then were challenged with pH1N1 at 3 weeks postboost (wpb). Another group was vaccinated with the same monovalent WIV and challenged at 6 wpb to determine if the time postvaccination plays a role in the development of VAERD. In a follow-up study, the impact of age of first WIV vaccination (at 4 versus 9 weeks of age) with a boost 3 weeks later (at 7 versus 12 weeks of age) was evaluated. A monovalent live-attenuated influenza virus (LAIV) vaccine administered at 4 and 7 weeks of age was also included. All mismatched WIV groups had significantly higher lung lesions than the LAIV, bivalent MN08-CA09, and control groups. Age of first vaccination or length of time between booster dose and subsequent challenge did not alter the development of VAERD in WIV-vaccinated pigs. Importantly, the mismatched component of the bivalent MN08-CA09 WIV did not override the protective effect of the matched vaccine component.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ignacio Callejas Caballero ◽  
Marta Illán Ramos ◽  
Arantxa Berzosa Sánchez ◽  
Eduardo Anguita ◽  
José Tomás Ramos Amador

Abstract Background Although neutropenia is relatively frequent in infants and children and is mostly a benign condition with a self-limited course, it can lead to life-threatening severe infections. Autoimmune neutropenia is a relatively uncommon hematological disorder characterized by the autoantibody-induced destruction of neutrophils. It is usually triggered by viral infections with very few documented cases after influenza virus. Case presentation An 8-month-old male infant presented at the emergency room with a 5-days history of fever up to 39.7 °C, cough and runny nose. In the blood test performed, severe neutropenia was diagnosed (neutrophils 109/μL). A nasopharyngeal aspirate revealed a positive rapid test for Influenza A. Serum antineutrophil antibodies were determined with positive results. Neutropenia targeted panel showed no mutations. Despite maintenance of severe neutropenia for 9 months the course was uneventful without treatment. Conclusions When severe neutropenia is diagnosed and confirmed, it is essential to rule out some potential etiologies and underlying conditions, since the appropriate subsequent management will depend on it. Although autoimmune neutropenia triggered by viral infections has been widely reported, it has seldom been reported after influenza infection. The benign course of the disease allows a conservative management in most cases.


2022 ◽  
Vol 67 (4) ◽  
pp. 203-213
Author(s):  
Suhaila N. Darogha ◽  
Sarhang H. Azeez ◽  
Zhian G. Abdullah

Urinary tract infection (UTI) is a major clinical problem in a wide age range that is associated with a high morbidity rate. Due to issues such as low specificity and the inability to differentiate between different types of infection in current diagnostic methods, there is a need to introduce novel UTI markers. The present study was conducted to evaluate the utility of Procalcitonin (PCT) and interleukin-6 (IL-6) as a marker of bacterial urinary tract infection. For this purpose, a cross-sectional study was conducted between November 2020 and February 2021 among 125 patients and 60 healthy volunteers (control) in Erbil Teaching Hospital. The concentration of PCT and IL-6 was quantified using the ELISA cloud immunoassay test. Between-group comparisons were assessed for the variables with analysis of variance. The results revealed that there was a significant difference between PCT levels in UTI patients (104.6±6.07) and control groups (54±2.24) (p <0.0001). The differences in IL-6 concentration in UTI patients (55.74±4.2) and control groups (24.56±2.4) were also significant (p <0.0001), implying that the level of both PCT and IL-6 increased due to bacterial infection in the urinary tract. As a whole, the findings of this study provide


2019 ◽  
Vol 71 (5) ◽  
pp. 1195-1203 ◽  
Author(s):  
Tim K Tsang ◽  
Kyu Han Lee ◽  
Betsy Foxman ◽  
Angel Balmaseda ◽  
Lionel Gresh ◽  
...  

Abstract Background Previous studies suggest that the nose/throat microbiome may play an important role in shaping host immunity and modifying the risk of respiratory infection. Our aim is to quantify the association between the nose/throat microbiome and susceptibility to influenza virus infection. Methods In this household transmission study, index cases with confirmed influenza virus infection and their household contacts were followed for 9–12 days to identify secondary influenza infections. Respiratory swabs were collected at enrollment to identify and quantify bacterial species via high-performance sequencing. Data were analyzed by an individual hazard-based transmission model that was adjusted for age, vaccination, and household size. Results We recruited 115 index cases with influenza A(H3N2) or B infection and 436 household contacts. We estimated that a 10-fold increase in the abundance in Streptococcus spp. and Prevotella salivae was associated with 48% (95% credible interval [CrI], 9–69%) and 25% (95% CrI, 0.5–42%) lower susceptibility to influenza A(H3N2) infection, respectively. In contrast, for influenza B infection, a 10-fold increase in the abundance in Streptococcus vestibularis and Prevotella spp. was associated with 63% (95% CrI, 17–83%) lower and 83% (95% CrI, 15–210%) higher susceptibility, respectively. Conclusions Susceptibility to influenza infection is associated with the nose/throat microbiome at the time of exposure. The effects of oligotypes on susceptibility differ between influenza A(H3N2) and B viruses. Our results suggest that microbiome may be a useful predictor of susceptibility, with the implication that microbiome could be modulated to reduce influenza infection risk, should these associations be causal.


2020 ◽  
Author(s):  
Ronghe Zhu ◽  
Cuie Chen ◽  
Qiu Wang ◽  
Xixi Zhang ◽  
Chaosheng Lu ◽  
...  

Abstract Purpose Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection. Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lukasz Kedzierski ◽  
Michelle D Tate ◽  
Alan C Hsu ◽  
Tatiana B Kolesnik ◽  
Edmond M Linossi ◽  
...  

Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rupak Desai ◽  
Jilmil S Raina ◽  
Vikram Itare ◽  
Akhil Jain ◽  
Sandeep Singh ◽  
...  

Introduction: Literature reported cardiac tamponade in patients with influenza virus infection, which incited us to understand patient-level demographics, courses and outcomes. Methods: Systematic literature search was performed until May 2020 to review post-influenza cardiac tamponade cases. Results: Twenty five publications reported 28 patients (M:F::12:15, age range: 4-69 yrs, 9 pediatric) who had post-influenza cardiac tamponade as shown in Table 1 . Nine (32.1%) patients had dyspnea and 7 (25%) had chest pain. Onset of tamponade after flu ranged from 1 day-6 weeks. 22 (78.5%) and 3 (10.7%) were infected with Influenza A and B strains respectively. Troponin-T (n=7) ranged from 0.03 ng/dL-10.50 ng/dL. Twelve (42.8%) patients were treated with influenza therapy; 8 (28.5%) with Pseltamivir, 2 (7.1%) with Oseltamivir followed by Peramivir, 1 (3.5%) with Zanamivir, 1 (3.5%) with Zanamivir followed by Peramivir. Pericardiocentesis was done in 25 (89.2%) patients. Seventeen (57.1%) patients required mechanical circulatory/respiratory support: 13 intubations, 3 ECMO, 2 CPR, 1 external defibrillation and 1 noninvasive ventilation. Twenty-three (82.1%) patients recovered while 4 (14.2%) patients died. Conclusion: This systematic review of patient-level data showed high recovery rate with early diagnosis and timely pericardiocentesis and nearly 14% of mortality rate.


2020 ◽  
Vol 18 ◽  
pp. 205873922094613
Author(s):  
Xuyun Peng ◽  
Yichun Xiao ◽  
Li Li ◽  
Dongxiang Wen ◽  
Xiaoyan Gong ◽  
...  

The data from a total of 200 children with suspected influenza virus infection were assessed at the febrile clinic of Women and Children’s hospital in Ganzhou of Jiangxi province from January 2018 to March 2019, and the patients were belonged to two groups (peramivir treatment group and oseltamivir treatment group). At the same time, 100 patients without special treatment were evaluated as the control group. We observed the patients’ fever relief time, pharyngeal pain relief time, nasal congestion relief time, runny nose symptoms relief time, days of hospitalization, days of medication, cost of medication, and adverse reactions in the three groups. We analyzed and compared the efficacy and adverse reactions of peramivir and oseltamivir in the treatment of children suspected with influenza. The recovery of body temperature, relief of cough, days of medication, and hospitalization period in the peramivir group were significantly shorter compared to the oseltamivir and control groups. The mean times to alleviation of fever in the three groups were 18.28 ± 17.74 h (peramivir group), 48.20 ± 34.28 h (oseltamivir group), and 72.56 ± 25.78 h (control group). The mean times to alleviation of cough in the three groups were 49.77 ± 27.58 h (peramivir group), 68.53 ± 32.54 h (oseltamivir group), and 59.38 ± 31.26 (control group). The cost of the peramivir group was significantly higher than that of the oseltamivir and control groups. The incidence of drug reactions in the peramivir group was significantly lower than that in the oseltamivir group. The rate of antibiotic usage in the peramivir group was significantly lower than that in the oseltamivir and control groups. Peramivir can significantly alleviate symptoms and reduce the use of antibiotics in children with suspected influenza. Peramivir has demonstrated good efficacy, high safety, and good compliance in treating children with suspected influenza infection.


Author(s):  
Ashleigh R. Murphy-Schafer ◽  
Silke Paust

Influenza A virus (IAV) is a respiratory pathogen that infects millions of people each year. Both seasonal and pandemic strains of IAV are capable of causing severe respiratory disease with a high risk of respiratory failure and opportunistic secondary infection. A strong inflammatory cytokine response is a hallmark of severe IAV infection. The widespread tissue damage and edema in the lung during severe influenza is largely attributed to an overexuberant production of inflammatory cytokines and cell killing by resident and infiltrating leukocytes. Mast cells (MCs) are a sentinel hematopoietic cell type situated at mucosal sites, including the lung. Poised to react immediately upon detecting infection, MCs produce a vast array of immune modulating molecules, including inflammatory cytokines, chemokines, and proteases. As such, MCs have been implicated as a source of the immunopathology observed in severe influenza. However, a growing body of evidence indicates that MCs play an essential role not only in inducing an inflammatory response but in suppressing inflammation as well. MC-derived immune suppressive cytokines are essential to the resolution of a number of viral infections and other immune insults. Absence of MCs prolongs infection, exacerbates tissue damage, and contributes to dissemination of the pathogen to other tissues. Production of cytokines such as IL-10 and IL-6 by MCs is essential for mitigating the inflammation and tissue damage caused by innate and adaptive immune cells alike. The two opposing functions of MCs—one pro-inflammatory and one anti-inflammatory—distinguish MCs as master regulators of immunity at the site of infection. Amongst the first cells to respond to infection or injury, MCs persist for the duration of the infection, modulating the recruitment, activation, and eventual suppression of other immune cells. In this review, we will discuss the immune modulatory roles of MCs over the course of viral infection and propose that the immune suppressive mediators produced by MCs are vital to minimizing immunopathology during influenza infection.


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