Interleukin-16 is increased in dialysis patients but is not a cardiovascular risk factor.

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort.

Investigation of serum IL-12, IL-16, and IL-17A as diagnostic biomarkers in children with cow’s milk protein allergy

Background Cow’s milk protein allergy (CMPA) is an abnormal immune response caused by milk proteins and is most common in infancy and early childhood. Statistics revealed up to 7.5% of children suffered from milk allergy. Its clinical symptoms were characterized by diversity, non-specificity, and can affect multiple systems, including the digestive tract, skin, and respiratory tract. In this study, we aimed to investigate the effects of IL-12, IL-16, and IL-17A on diagnosing and monitoring CMPA in children for clinical treatment.Methods A total of 158 infants with CMPA and 89 healthy babies were recruited and evaluated. Demographic and clinical information of all participants were recorded. An extensive analysis of inflammatory cytokine levels, including IL-12, IL-16, and IL-17A, was performed in blood samples from 247 infants younger than 9 months. Meanwhile, the serological specificity immunoglobulin E (sIgE) levels were evaluated. In addition, the area under the curve (AUC) values of IL-12, IL-16, and IL-17A in differentiating CMP from healthy babies were measured by receiver operating characteristic analysis. Finally, the correlation between sIgE and IL-12, IL-16, and IL-17A levels were detected using Spearman correlation analysis.Results Compared with healthy control, infants who developed CMPA had decreased IL-12, increased IL-16, and IL-17A. Moreover, a significant correlation between serum IL-12, IL-16, IL-17A and sIgE levels was observed in the CMPA group. In addition, AUC values of IL-12, IL-16, and IL-17A in discriminating CMPA from healthy infants were 0.8425, 0.9196, and 0.8813, respectively. Finally, IL-12 was increased while IL-16 and IL-17A levels were decreased in the CMPA group after three months of milk avoidance treatment.Conclusions We found that IL-12, IL-16, and IL-17A levels in children with CMPA were associated with SCORAD scores, sIgE levels (AU)

Correlation of Serum Levels of Interleukine-16, CCL27, Tumor Necrosis Factor-related Apoptosis-inducing Ligand, and B-cell Activating Factor with Multiple Sclerosis Severity.

The pathogenic roles of Interleukine-16 (IL-16), CCL27, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and B-cell activating factor (BAFF) has been shown in some autoimmune and inflammatory diseases. We aimed to correlate the circulatory changes of such factors with the severity of disease in patients with multiple sclerosis (MS). This case-control study was conducted on 84 MS patients and 83 healthy controls. We measured the serum levels of IL-16, CCL27, TRAIL, and BAFF in all participants by enzyme-linked immune sorbent assay. Using the expanded disability status scale (EDSS), we evaluated the severity of MS. Finally, we assessed the correlation between serum levels of such factors with the severity of MS. We found increased serum levels of CCL27, IL-16, and BAFF in patients with MS compared to those in healthy subjects. However, no difference was found in serum levels of TRAIL between the patients and controls. In addition, a significant positive correlation between serum levels of CCL27, IL-16, TRAIL, and BAFF with disease severity according to EDSS score was determined. We showed higher serum levels of CCL27, BAFF, TRAIL, and IL-16 in MS patients with more severe disabilities than mild forms. Such finding may represent their contribution to the pathogenesis of MS. Blocking such molecules may yield new treatments for MS.

Serum Inflammatory Factor Profiles in the Pathogenesis of High-Altitude Polycythemia and Mechanisms of Acclimation to High Altitudes.

High-altitude polycythemia (HAPC) is a common aspect of chronic mountain sickness (CMS) caused by hypoxia and is the main cause of other symptoms associated with CMS. However, its pathogenesis and the mechanisms of high-altitude acclimation have not been fully elucidated. Exposure to high altitude is associated with elevated inflammatory mediators. In this study, the subjects were recruited and placed into a plain control (PC) group, plateau control (PUC) group, early HAPC (eHAPC) group, or a confirmed HAPC (cHAPC) group. Serum samples were collected, and inflammatory factors were measured by a novel antibody array methodology. The serum levels of interleukin-2 (IL-2), interleukin-3 (IL-3), and macrophage chemoattractant protein-1 (MCP-1) in the eHAPC group and the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, tumor necrosis factor-alpha (TNF-alpha), MCP-1, and interleukin-16 (IL-16) in the cHAPC group were higher than those in the PUC group. More interestingly, the expression of IL-1 beta, IL-2, IL-3, TNF-alpha, MCP-1, and IL-16 in the PUC group showed a remarkable lower value than that in the PC group. These results suggest that these six factors might be involved in the pathogenesis of HAPC as well as acclimation to high altitudes. Altered inflammatory factors might be new biomarkers for HAPC and for high-altitude acclimation.

Association of IL16 polymorphisms with periodontitis in Brazilians: A case- control study.

Periodontitis (PD) is a chronic inflammatory process resulting from the relationship of the immune response with the components in dental plaque. Cytokines and their genetic polymorphisms seem to be involved in the immunopathogenesis of this disease. This study aimed to evaluate the correlation of IL16 polymorphism with PD. A case-control study was conducted in a sample of individuals from southern Brazil. The genotyping of IL16, rs11556218 T>G, rs4072111 C>T e rs4778889 T>C, was performed using the PCR-RFLP methodology. The serum level of IL-16 was determined using an IL-16 ELISA kit for humans. SNPStats and OpenEpi software and Wilcoxon's U test were used to perform statistical analysis. IL16 rs11556218 polymorphism was significantly associated to PD in nonsmoking patients: individuals with G/G genotype were less likely to develop PD compared to the T/T genotype (OR = 0.10; Pc = 0.019, codominant model). In addition, the TTT haplotype was associated with a high risk for PD (OR = 2.45; P = 0.01). A low IL-16 serum level was observed among individuals with PD when compared to controls (P = 0.027). Thus, the IL16 rs16556218 polymorphism and the serum levels of IL-16 were associated with periodontitis in a Brazilian sample, and this was influenced by environmental factors such as smoking.

IL-38 inhibits microglial inflammatory mediators and is decreased in amygdala of children with autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by impaired social interactions and communication. The pathogenesis of ASD is not known, but it involves activation of microglia. We had shown that the peptide neurotensin (NT) is increased in the serum of children with ASD and stimulates cultured adult human microglia to secrete the proinflammatory molecules IL-1ß and CXCL8. This process is inhibited by the cytokine IL-37. Another cytokine, IL-38, has been reported to have antiinflammatory actions. In this report, we show that pretreatment of cultured adult human microglia with recombinant IL-38 (aa3-152, 1-100 ng/mL) inhibits (P < 0.0001) NT-stimulated (10 nM) secretion of IL-1ß (at 1 ng/mL) and CXCL8 (at 100 ng/mL). In fact, IL-38 (aa3-152, 1 ng/mL) is more potent than IL-37 (100 ng/mL). Here, we report that pretreatment with IL-38 (100 ng/mL) of embryonic microglia (HMC3), in which secretion of IL-1ß was undetectable, inhibits secretion of CXCL8 (P = 0.004). Gene expression of IL-38 and its receptor IL-36R are decreased (P = 0.001 and P = 0.04, respectively) in amygdala from patients with ASD (n = 8) compared to non-ASD controls (n = 8), obtained from the University of Maryland NeuroBioBank. IL-38 is increased (P = 0.03) in the serum of children with ASD. These findings indicate an important role for IL-38 in the inhibition of activation of human microglia, thus supporting its development as a treatment approach for ASD.

Serum interleukin-16 significantly correlates with the Vasculitis Damage Index in antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: Interleukin (IL)-16 is a T cell chemoattractant produced by peripheral mononuclear cells. We investigated whether IL-16 plays a pro- or an anti-inflammatory role in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Furthermore, we investigated whether the level of IL-16 could predict the activity and extent of organ damage in AAV based on AAV-specific indices. METHODS: Seventy-eight patients with AAV from a prospective observational cohort were included in this analysis. Blood sampling and clinical assessments, including the Birmingham Vasculitis Activity Score (BVAS), Five-Factor Score (FFS), Short Form 36-item Health Survey (SF-36), and Vasculitis Damage Index (VDI), were performed, and laboratory data were collected. Serum IL-16 was measured from stored sera. RESULTS: The median age was 62.0 years, and 27 patients were male. The median serum IL-16 concentration was 84.1 pg/dL, and the median BVAS, FFS, VDI, and SF-36 scores were 7.0, 1.0, 3.0, and 48.0, respectively. Among the AAV-related indices, the serum IL-16 concentration was correlated with VDI (R2 = 0.306, P = 0.006), but not with BVAS (R2 = 0.024, P = 0.834), FFS (R2 = - 0.069, P = 0.550), or SF-36 (R2 = - 0.015, P = 0.898). The serum IL-16 concentration also did not correlate with either the erythrocyte sedimentation rate or the C-reactive protein concentration. Per our analysis based on organ involvement, only patients with ear, nose, and throat manifestations had higher serum IL-16 concentrations relative to those with other conditions (P = 0.030). CONCLUSIONS: This was the first study to elucidate the clinical implication of serum IL-16 in patients with AAV. We found that the serum IL-16 level may reflect the cross-sectional VDI scores among AAV-specific indices. Future studies with larger numbers of patients and serial measurements could provide more reliable data on the clinical implications of serum IL-16 in AAV.

IL-16 expression is increased in the skin and sera of patients with systemic sclerosis.

OBJECTIVES: SSc is an autoimmune disease with chronic and persistent inflammation in its pathogenesis. To examine the expression pattern of IL-16 in SSc lesions, the serum concentration of IL-16 in SSc patients and the relationship between serum IL-16 levels and the clinical symptoms of SSc were investigated. METHODS: Using immunohistochemical analysis, we examined the quantity and localization of IL-16 in affected skin obtained from SSc patients. We also measured serum levels of IL-16 in SSc patients using an ELISA. We then validated the correlation between serum IL-16 levels and clinical symptoms in patients with SSc. RESULTS: In the skin, IL-16 was expressed on the lymphocytes around the capillaries. Furthermore, the proportion of IL-16-positive cells was statistically higher in patients with dcSSc than in those with lcSSc patients (43.9 vs 29.1%, P < 0.05). The serum IL-16 levels in SSc patients were statistically significant elevated compared with healthy controls (297.0 vs 194.9 pg/ml, P < 0.05). Increased serum IL-16 levels in SSc patients were correlated with the proportion classified as dcSSc, skin score and the presence of cutaneous symptoms of erythema and pigmentation. CONCLUSION: The regional up-regulation of IL-16 in the skin is not only associated with skin sclerosis, but also with systemic IL-16 activation. IL-16 may play a role in the pathogenesis of SSc. Moreover, serum IL-16 levels may be useful as a biomarker for determining the severity of the skin sclerosis. Inhibiting IL-16 activation may be effective in treating SSc.

High-Dose Dexamethasone Alters the Increase in Interleukin-16 Level in Adult Immune Thrombocytopenia.

Adult primary immune thrombocytopenia (ITP) is an autoimmune-mediated haemorrhagic disorder. Interleukin-16 (IL-16) can directly affect cellular or humoural immunity by mediating the cellular cross-talk among T cells, B cells and dendritic cells. Several studies have focused on IL-16 as an immunomodulatory cytokine that takes part in Th1 polarization in autoimmune diseases. In this study, we investigated IL-16 expression in the bone marrow supernatant and plasma of ITP patients and healthy controls. What's more, we detected IL-16 expression in ITP patients with the single-agent 4-day high-dose dexamethasone (HD-DXM) therapy. In patients with active ITP, bone marrow supernatant and plasma IL-16 levels increased (P < 0.05) compared with those of healthy controls. In the meantime, the mRNA expression in BMMCs (pro-IL-16, caspase-3) and PBMCs (pro-IL-16, caspase-3 and T-bet) of ITP patients was increased (P < 0.05) relative to those of healthy controls. In patients who responded to HD-DXM therapy, both plasma IL-16 levels and gene expression in PBMCs (pro-IL-16, caspase-3, and T-bet) were decreased (P < 0.05). In summary, the abnormal level of IL-16 plays important roles in the pathogenesis of ITP. Regulating Th1 polarization associated with IL-16 by HD-DXM therapy may provide a novel insight for immune modulation in ITP.

Donepezil Attenuates Obesity-Associated Oxidative Stress and Central Inflammation and Improves Memory Deficit in Mice Fed a High-Fat Diet.

BACKGROUND/AIMS: Obesity is associated with chronic inflammation and cognitive decline, and is considered a major risk factor for neurodegeneration. Meanwhile, neuroinflammation is important in the pathogenesis and progression of neurodegenerative diseases. METHODS: In this study, we tested the hypothesis that donepezil would attenuate central inflammation and oxidative damage and improve memory deficit in high-fat diet (HFD)-fed mice. After 16 weeks on a HFD, C57BL/6J mice were given either donepezil (3 mg/kg, i.p.) or saline for 4 weeks in parallel to a control diet (CD) group. Thereafter, the step-through test was used to assess learning and memory function. RESULTS: In the brain of HFD-fed mice, levels of the proinflammatory cytokines interleukin 16 and tumor necrosis factor α were reduced by donepezil treatment. Similarly, HFD-induced protein levels of advanced glycation end-products and oxidative stress in the brain were significantly decreased by donepezil treatment. CONCLUSION: Our results indicate that donepezil may reverse obesity-related central inflammation and oxidative damage and improve memory deficit in HFD-fed mice.

Elevated IL-16 expression is associated with development of immune dysfunction in children with autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in communication skills and social behaviors. Several studies have suggested that neuroimmune dysfunction plays a significant role in the pathogenesis of ASD; however, its exact etiology is unknown. Interleukin-16 (IL-16), a chemoattractant, is associated with various inflammatory processes. However, its role in children with ASD is unclear. This study aimed to investigate whether IL-16 expression is associated with immune dysfunction in children with ASD. We examined IL-16 expression in CD4+, CD8+, CD14+, CCR3+, and CXCR7+ cells in typically developing (TD) controls and children with ASD using flow cytometry in peripheral blood mononuclear cells (PBMCs). We also investigated the expression of IL-1ß+IL-16+, IL-6+IL-16+, and TNF-α+IL-16+ in TD controls and children with ASD. We further explored IL-16 mRNA and protein expression using RT-PCR and western blotting. CD4+IL-16+, CD8+IL-16+, CD14+IL-16+, CCR3+IL-16+, and CXCR7+IL-16+ cells increased significantly in children with ASD compared with TD controls. We also showed that expression of IL-1ß+IL-16+, IL-6+IL-16+, and TNF-α+IL-16+ was elevated in children with ASD compared with TD controls. Moreover, IL-16 mRNA and protein expression was significantly induced in children with ASD compared with TD controls. These results suggest that IL-16 expression could play an essential role in immune alteration in children with ASD.

Role of soluble inflammatory mediators and different immune cell populations in early control of symptomatic acute hepatitis C virus infection.

The natural course of acute Hepatitis C Virus (aHCV) infection is highly heterogeneous, and only few biomarkers have been identified to reliably predict the outcome of infection. We analysed a large panel of soluble inflammatory mediators, immune cell frequencies and phenotypes using peripheral blood samples from 26 patients with symptomatic aHCV infection from a controlled randomized clinical trial (ISRCTN88729946, www.isrctn.com). We found that patients with a spontaneous early HCV control demonstrated a distinct expression pattern of various soluble immune mediators including IFNα and IL-16. Immune cell phenotype and frequency differed between patients who cleared the viral infection early (n=13) and those who remained HCV RNA positive after 12 weeks of observation (n=13) with a reduced ratio of CD4+ T cells to NK cells in the non-early clearer. Further, correlation analyses of 50 cytokines and chemokines revealed more positive correlations in between the distinct cytokines, especially for IFNα and IL-16, and between the cytokines and HCV RNA levels in spontaneous early clearer patients. Beyond that, in vitro stimulation of CD4+ T cells with IL-16 reduced the susceptibility of these cells to killing by IFNα-activated NK cells. These data indicate that the immune cell composition and cytokine pattern varies considerably in patients with symptomatic aHCV infection. NK cell-mediated killing of CD4+ T cells might affect early control of HCV infection.

Serially measured pre-diagnostic levels of serum cytokines and risk of brain cancer in active component military personnel.

BACKGROUND: There is growing evidence that history of allergic or autoimmune disease is associated with reduced risk of glioma, but few prospective studies have explored the biological basis. To assess associations with immune conditions and levels of 14 cytokines in serial prediagnostic serum samples, we conducted a study of glioma/brain cancer nested in a cohort of active component military personnel. METHODS: A total of 457 case-control sets were ascertained from the Department of Defense (DoD) Automated Central Tumour Registry, Defense Medical Surveillance System (DMSS) database, and DoD Serum Repository. These were individually matched on sex, race/ethnicity, birth year, number of serum samples (1, 2 or 3), and date(s) of sample collection. We obtained diagnoses of pre-existing immune-related conditions from the DMSS database and measured cytokines using Meso Scale Discovery assays. Statistical analyses included conditional logistic regression. RESULTS: Overall association between glioma and prior immune-related conditions was null. Higher levels of IL-15 and IL-16 were independently associated with lower glioma risks (Ptrend = 0.002 and Ptrend = 0.001); both associations were more pronounced in individuals with prior immune conditions (Pheterogeneity = 0.0009 and Pheterogeneity = 0.031). CONCLUSIONS: Associations with pre-diagnostic levels of IL-15 and IL-16 and their modification by diagnosis of immune-related conditions support the importance of immune alterations in glioma aetiology years before diagnosis.

Validation of Raised Cord Blood Interleukin-16 in Perinatal Asphyxia and Neonatal Hypoxic-Ischaemic Encephalopathy in the BiHiVE2 Cohort.

The role of inflammation is an important factor in the progression of hypoxic-ischaemic encephalopathy (HIE). We have previously shown that interleukin-16 (IL-16) is increased in infants with moderate and severe HIE and relates to poor neurodevelopmental outcomes. We aimed to validate IL-16 as a cord blood-based biomarker for HIE and to examine its relationship to long-term outcomes. The study sample consisted of 105 full-term infants who experienced perinatal asphyxia (PA) (with and without an encephalopathy) along with healthy, gestational age-matched newborn controls. Umbilical cord blood serum was processed and biobanked at delivery. Infants were assigned a modified Sarnat score at 24 h. Analysis of IL-16 cytokine cord blood levels was performed using the sandwich-based enzyme-linked immunosorbent assay (ELISA) technique. Cord blood-based IL-16 was increased in infants with PA and HIE relative to controls (p = 0.025). IL-16 was also increased in the HIE group relative to controls (p = 0.042). There was no significant difference in IL-16 across grades of HIE or in those with abnormal outcomes at 2 years of age. This study validates findings that cord blood-based IL-16 levels are increased in infants with PA, including those who go on to develop HIE.

Prospective evaluation of serum IL-16 and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: Sexually transmitted infections and chronic inflammation have been associated with an increased risk of prostate cancer. Inflammatory mediators, such as cytokines and free radicals, have been hypothesized to play a role. METHODS: To explore the role of inflammation in prostate cancer risk further, we examined the association between pre-diagnostic serum levels of interleukin-16 (IL-16), an important pleiotropic cytokine, and prostate cancer risk among 932 Caucasian cases and 942 controls and 154 African-American cases and 302 controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum IL-16 was quantified using enzyme-linked immunoassay. Logistic regression was used to estimate associations between IL-16 and prostate cancer risk, separately by race. RESULTS: Although no association between IL-16 and prostate cancer overall was observed among Caucasians (p = 0.27), a significantly increased risk of high-grade prostate cancer, defined as Gleason ≥ 7 (phet = 0.02), was observed with increasing levels of IL-16 (OR3rd vs. 1st tertile = 1.37, 95% CI 1.04-1.81, ptrend = 0.02). We also discovered a significant interaction between IL-16 and history of gonorrhea (p = 0.04). Among Caucasian men with a history of gonorrhea, elevated IL-16 levels were associated with an increased risk of prostate cancer (OR3rd vs. 1st tertile = 3.64, 95% CI 1.14-11.6) but no association was seen among those without a history of gonorrhea (OR3rd vs. 1st tertile = 1.06, 95% CI 0.83-1.34). No associations were observed among African-Americans. CONCLUSIONS: This study found evidence that higher pre-diagnostic IL-16 levels may be associated with increased risk of high-grade disease, supporting inflammation as potential mechanism by which sexually transmitted diseases may increase risk.

IL8 and IL16 levels indicate serum and plasma quality.

BACKGROUND: Longer pre-centrifugation times alter the quality of serum and plasma samples. Markers for such delays in sample processing and hence for the sample quality, have been identified. METHODS: Twenty cytokines in serum, EDTA plasma and citrate plasma samples were screened for changes in concentration induced by extended blood pre-centrifugation delays at room temperature. The two cytokines that showed the largest changes were further validated for their "diagnostic performance" in identifying serum or plasma samples with extended pre-centrifugation times. RESULTS: In this study, using R&D Systems ELISA kits, EDTA plasma samples and serum samples with a pre-centrifugation delay longer than 24 h had an IL16 concentration higher than 313 pg/mL, and an IL8 concentration higher than 125 pg/mL, respectively. EDTA plasma samples with a pre-centrifugation delay longer than 48 h had an IL16 concentration higher than 897 pg/mL, citrate plasma samples had an IL8 concentration higher than 21.5 pg/mL and serum samples had an IL8 concentration higher than 528 pg/mL. CONCLUSIONS: These robust and accurate tools, based on simple and commercially available ELISA assays can greatly facilitate qualification of serum and plasma legacy collections with undocumented pre-analytics.

Elevated plasma levels of interleukin-16 in patients with acute myocardial infarction.

Interleukin (IL)-16, a polypeptide cytokine, plays a crucial role in the inflammatory process, acting as a chemoattractant for peripheral immune cells and has been linked to various inflammatory diseases. However, its role in patients with acute myocardial infarction (AMI) is unclear.We retrospectively analyzed serum levels of IL-16 in blood of patients with (STEMI, n = 45) and without ST-segment elevation myocardial infarction (NSTEMI, n = 42) compared with controls with excluded coronary artery disease (n = 55). Furthermore, correlation analysis with inflammatory cells, C-reactive protein (CRP) levels, dendritic cell precursors (DCPs), and other clinical and biochemical markers was performed.Compared with controls, patients with STEMI and NSTEMI evidenced higher levels of IL-16 in pg/mL (STEMI: 759.38 ±â€Š471.54, NSTEMI: 677.77 ±â€Š438.8, control: 500.45 ±â€Š432.21; P = .002). IL-16 correlated with CRP (r = 0.26, P = .001), leucocytes (r = 0.38, P < .001), NT-proBNP (r = 0.20, P = .02) and hsTnT (r = 0.25, P = .004). Circulating myeloid DCPs, plasmacytoid DCPs, and total DCPs showed a significant inverse correlation to IL-16 levels (r = -0.21, P = .01; r = -0.23, P = .005; r = -0.26, P = .002, respectively).Interleukin-16 might play an important role in the inflammatory process of patients suffering from AMI and correlates with inflammatory cell activation and clinical and biochemical markers. The cytokine IL-16 might upregulate the proinflammatory response and recruitment of inflammatory cells into infarcted myocardium.

Diagnostic and prognostic value of serum interleukin­16 in patients with gastric cancer.

Gastric cancer (GC) is one of the major leading causes of cancer­associated mortality worldwide. Serum biomarkers have a vital role in diagnosis and prognosis of GC, and interleukin (IL)­16 may serve as a useful biomarker with prognostic value for human cancers. The current study aimed to evaluate the expression level of serum IL­16 in patients with GC, and evaluate the diagnostic and prognostic value of IL­16. ELISA was performed determine the serum IL­16 levels in patients with GC and healthy controls. Receiver operator curve analysis was performed to evaluate the diagnostic and prognostic potential value of serum IL­16 in GC diagnosis. Migration and invasion assays were performed using cells with IL­16 small interfering RNA (siRNA) knockdown. The results demonstrated that serum IL­16 levels were significantly higher in GC samples than in healthy controls, and increased serum IL­16 levels were significantly associated with tumor recurrence and poor prognosis. Knockdown of IL­16 significantly suppressed the migration and invasion of GC cells. In conclusion, the current results indicate that serum IL­16 levels may have diagnostic and prognostic value for patient with GC.

Cord Blood IL-16 Is Associated with 3-Year Neurodevelopmental Outcomes in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy.

Activation of the inflammatory pathway is increasingly recognized as an important mechanism of injury following neonatal asphyxia and encephalopathy. This process may contribute to the poor prognosis seen in some cases, despite therapeutic hypothermia. Our group has previously identified raised interleukin (IL)-6 and IL-16, measured in umbilical cord blood at birth, to be predictive of grade of hypoxic-ischaemic encephalopathy (HIE). Our aim in this study was to examine the ability of these cytokines to predict the 3-year neurodevelopmental outcome in the same cohort. As part of a prospective, longitudinal cohort study set in a single tertiary maternity unit, term infants with biochemical and clinical evidence of perinatal asphyxia were recruited at birth. Umbilical cord blood was collected and analyzed for IL-6 and IL-16 using a Luminex assay. The neurodevelopmental outcome of these infants was assessed at 3 years using the Bayley Scales of Infant and Toddler Development (Edition 3). Early cord blood measurement of IL-6 and IL-16 and long-term outcome were available in 33/69 infants. Median (IQR) IL-16 differentiated infants with a severely abnormal outcome (n = 6) compared to all others (n = 27), (646 [466-1,085] vs. 383.5 [284-494] pg/mL; p = 0.012). IL-16 levels were able to predict a severe outcome with an area under the receiver-operating characteristic (ROC) curve of 0.827 (95% CI 0.628-1.000; p = 0.014). Levels ≥514 pg/mL predicted a severe outcome with a sensitivity of 83% and a specificity of 81%. IL-16 also outperformed other routine biochemical markers available at birth for the prediction of severe outcome. APGAR scores at 1 and 10 min were also predictive of a severe outcome (p = 0.022 and p = 0.036, respectively). A combination of IL-16 with these clinical markers did not improve predictive value, but IL-16 combined with electroencephalogram grading increased the area under the ROC curve. IL-6 did not show any association with 3-year outcome. This is the first report studying the association of IL-16 measured at birth with long-term outcome in a cohort of neonates with perinatal asphyxia. IL-16 may be an early biomarker of severe injury and aid in the long-term prognostication in infants with HIE.