Level of Interleukin-35, Interleukin-36, and the Interleukin-35/Interleukin-36 Ratio in Juvenile Idiopathic Arthritis

BACKGROUND: Cytokines are inflammatory mediators that regulate multiple processes potentially implicated in inflammation and autoimmunity. AIM: This study aimed to investigate the levels of circulating interleukin (IL)-35, IL-36, and IL-35/IL-36 ratio in Juvenile Idiopathic Arthritis (JIA) patients. METHODS: Fifty-one patients categorized based on the International League of Associations for Rheumatology classification criteria were enrolled, along with 46 healthy controls. Disease activity assessment was conducted according to the Juvenile Arthritis Disease Activity Score (JADAS-27) system. Serum cytokine levels were determined using the sandwich enzyme-linked immunosorbent assay. RESULTS: Compared to controls, the serum levels of IL-36 were significantly higher among JIA children (p = 0.002), and serum IL-35 levels and the IL-35/IL-36 ratio were significantly lower in the patients (p = 0.002, p < 0.001, respectively). Furthermore, the IL-35/IL-36 serum ratio, but not the absolute IL levels, correlated positively with the JADAS-27, giving a good indication of the disease outcome. Further, the IL-35/IL-36 serum ratio showed higher sensitivity and specificity compared to the absolute cytokine levels. CONCLUSION: A significant change in the circulating IL-35 and IL-36 levels and an imbalance in the IL35/IL36 ratio occur in JIA. This study is a novel attempt to explore the role of IL-35 and IL-36 in JIA; further studies are required to support our results. The IL-35/Il-36 ratio is a promising immunological marker to predict, diagnose, and monitor JIA.

Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum

Data on the quantification of the potentially neurotrophic adipo-myokine METRNL (Meteorin-like protein) in human cerebrospinal fluid (CSF) are lacking and migration of this secreted protein across the blood–brain barrier (BBB) is uncertain. In the present pilot study, METRNL concentrations were quantified by ELISA in paired serum and CSF samples of 260 patients (107 males, 153 females) undergoing neurological evaluation. METRNL was abundant in serum (801.2 ± 378.3 pg/mL) and CSF (1007.2 ± 624.2 pg/mL) with a CSF/serum ratio of 1.4 ± 0.8. Serum METRNL levels were significantly correlated (rho = +0.521) to those in CSF. CSF METRNL concentrations were significantly correlated (rho = +0.480) with albumin CSF/serum ratios. The CSF/serum ratios of METRNL and albumin were positively correlated in Reibergram analysis (rho = 0.498), indicating that raising CSF concentrations of METRNL are mediated by increasing BBB dysfunction. The CSF concentrations of METRNL strongly increased in a stepwise manner along with increasing BBB dysfunction from grade 0 to grade 3 and with rising CSF cell count. CSF/serum ratio of METRNL also increased from grade 0 (1.2 ± 0.7) to grade 3 (3.0 ± 0.2). Furthermore, CSF levels were positively correlated with age. In conclusion, METRNL is a secreted and neurotrophic myokine that crosses over the BBB. CSF concentrations of METRNL increase with BBB dysfunction.

Alveolar compartmentalization of inflammatory and immune cell biomarkers in pneumonia-related ARDS

Background Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes. Methods Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls. Results Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8+ lymphocytes PD-1 expression and hospital mortality. Conclusions IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.

The correlation between serum TG/HDL-c ratio and arterial stiffness using the cardio-ankle vascular index in overweight or obese patients

The effect of increasing TG/HDL-c serum ratio, as a result of insulin resistance, is considered to have an important role in the occurrence of arterial stiffness. Increased arterial stiffness is an important marker in the development of cardiovascular disease and is a predictor of heart attack and stroke. This research aims to determine the relationship between the arterial stiffness assessed through non-invasive cardio-ankle vascular index (CAVI) examination and the TG/HDL-c ratio in overweight and obese individuals. Cardio-Ankle Vascular Index (CAVI) is a non-invasive clinical measurement to evaluate arterial stiffness manner and independent of blood pressure. This is a correlational study with purposive sampling technique. Thirty-two subjects participated in this research and each subject underwent a CAVI examination to assess arterial stiffness and their blood samples were collected for lipid profile measurement. The data were analysed using Pearson Correlation Test. There was a positive and significant correlation between TG/HDL-c serum level and arterial stiffness using Cardio- Ankle Vascular Index (CAVI) in overweight or obese patients (p <0,01).

Water- and Fat-Soluble Antioxidants in Human Seminal Plasma and Serum of Fertile Males

Reactive oxygen species (ROS) are physiologically involved in functions like sperm maturation, capacitation and acrosome reaction, but their excess is involved in male infertility. Antioxidants in seminal plasma (SP) are an important factor balancing physiologic and harmful ROS activities. In this study, we determined and compared the full profiles of the water- and fat-soluble antioxidants in SP and serum of 15 healthy fertile subjects (ranging between the ages of 35 and 42 years). Ejaculates were obtained after 2–5 days of sexual abstinence. After liquefaction and withdrawal of an aliquot for the sperm count, samples were centrifuged to obtain SP. Thirty min after semen donation, a venous blood sample was collected from each subject. Donors with lower SP concentrations of ascorbic acid (n = 5) or α-tocopherol (n = 5) received a 4 week oral administration of either vitamin C (100 mg/day) or vitamin E (30 mg/day). They were then re-assayed to determine the SP and serum levels of ascorbic acid and α-tocopherol. SP and serum samples were properly processed and analyzed by HPLC methods suitable to determine water (ascorbic acid, glutathione (GSH) and uric acid) and fat-soluble (all-trans-retinoic acid, all-trans-retinol, α-tocopherol, carotenoids and coenzyme Q10) antioxidants. Data demonstrate that only ascorbic acid is higher in SP than in serum (SP/serum ratio = 4.97 ± 0.88). The other water-soluble antioxidants are equally distributed in the two fluids (GSH SP/serum ratio = 1.14 ± 0.34; uric acid SP/serum ratio = 0.82 ± 0.12). All fat-soluble antioxidants are about 10 times less concentrated in SP than in serum. In donors treated with vitamin C or vitamin E, ascorbic acid and α-tocopherol significantly increased in both fluids. However, the SP/serum ratio of ascorbic acid was 4.15 ± 0.45 before and 3.27 ± 0.39 after treatment, whilst those of α-tocopherol were 0.11 ± 0.03 before and 0.10 ± 0.02 after treatment. The results of this study, by showing the peculiar composition in water- and fat-soluble antioxidants SP, indicate that it is likely that still-unknown mechanisms allow ascorbic acid accumulation in SP against a concentration gradient. SP mainly relies its defenses on water- rather than fat-soluble antioxidants and on the mechanisms ensuring their transfer from serum.

URINOTHORAX: AN UNUSUAL CAUSE OF MASSIVE PLEURAL EFFUSION

A 74 year-old male with a history of high blood pressure and hyperuricemia was admitted to the hospital with asthenia, unquantified weight loss, dyspnea on moderate exertion for 2 weeks, and diffuse abdominal pain. Blood leukocyte count was 12400/uL, creatinine 0.98 mg/dL, CRP 19 mg/dL, and LDH 318 U/L. The chest X-ray showed a right pleural effusion and the pleural fluid was suggestive of an exudate. Thorax and abdominal CT scan revealed a polycystic right kidney with grade IV hydronephrosis and suggested the presence of a nephropleural fistula. The thoracocentesis was repeated and the pleural fluid / serum ratio of creatinine obtained was higher than 1 (1.35 mg/dL), which is a diagnostic criterion for urinothorax. Finally, a retrograde pyelography was carried out, and confirmed the passage of urinary tract fluid into the pleural cavity. A thoracic drainage tube and a nephrostomy through the superior calyx were placed, both draining purulent material. One month later, the control CT shows a right atrophic kidney and a reduction of the size of the fistulous path. Urinothorax is an infrequent and underdiagnosed pathology, with few cases reported. It is usually presented as a transudative pleural effusion. Currently, no test is available to confirm the diagnosis, although the ratio of serum creatinine/pleural creatinine could suggest the presence of urinothorax. Radiographic imaging is useful to support the diagnosis. Management of a urinothorax requires a multidisciplinary approach with an emphasis on the correction of the underlying urinary tract pathology, and once corrected, this often leads to a rapid resolution of the pleural effusion.