Relevant Research of Inflammatory Cytokines Spectrum in Peripheral Blood of Sudden Hearing Loss.

OBJECTIVE: To investigate whether there is a correlation between the inflammatory state and the pathogenesis and clinical features of sudden hearing loss (SHL) by studying the expression of inflammation-related cytokines in the peripheral blood of patients with SHL. METHODS: In this work, we analyzed the cytokine profiles of 48 analytes in 38 patients with SHL compared to 38 healthy donors using a multiplex immunoassay. This study used appropriate statistical methods to screen for inflammatory cytokines associated with the pathogenesis of SHL, to analyze their network correlation, and to analyze the relationship between clinical features of SHL and inflammatory cytokines. RESULTS: Several cytokines, including CTACK, Eotaxin, HGF, INF-α2, IFN-ß, IL-1ß, IL-1ra, IL-2Rα, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12(p40), IL-13, MIG, ß-NGF, SCF, and TNF-α, exhibited significantly higher levels in the peripheral blood of the SHL group compared to the control group. An inflammatory network composed of multiple cytokines, including IL-1ß, is a risk factor for the development of SHL. CONCLUSION: This study identified several inflammatory cytokines with elevated expression, which may be linked with the onset of SHL. The results of this study also provide a basis for the theoretical hypothesis of inflammation in SHL. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3293-3301, 2024.

Proteasome Subunit Alpha Type-7 Expression Suppresses Cutaneous Squamous Cell Carcinoma Progression by Inhibiting Cancer-associated Cytokines.

BACKGROUND/AIM: Cutaneous squamous cell carcinoma (cSCC) is a common non-melanoma skin cancer, and its incidence is increasing. Proteasome subunit alpha type-7 (PSMA7) has been found to be aberrantly expressed in several cancers. However, whether it functions as a tumor suppressor or oncogene in the pathogenesis of cancers, particularly cSCC, remains controversial. Here, we aimed to investigate the functions of PSMA7 in cSCC pathogenesis. PATIENTS AND METHODS: Clinicopathological characteristics were evaluated in 131 patients with cSCC using tissue sections. The expression of PSMA7, nucleotide-binding oligomerization domain-containing protein 1 (NOD1), and mitochondrial antiviral signaling protein (MAVS) was determined in cSCC tissue sections using immunohistochemical staining. The effect of PSMA7 expression on the biological behavior of cSCC cells was investigated in vitro. RESULTS: High immunoreactivity of PSMA7 (high-PSMA7) was detected in 53 (40.5%) patients with cSCC and was significantly associated with histologic grade (p=0.008) and favorable recurrence-free survival (p=0.018). The expression of PSMA7 and NOD1 (p=0.026) and MAVS (p=0.032) was negatively correlated in cSCC tissues. Contrary to the results of the cohort study, cell viability and invasiveness significantly decreased after PSMA7 down-regulation in cSCC cells in vitro. mRNA expression of tumor necrosis factor-alpha, interleukin-1 alpha (IL-1α), IL-6, and IL-8 were significantly increased after PSMA7 down-regulation in cSCC cells (all p=0.002). CONCLUSION: PSMA7-mediated degradation of NOD1 and MAVS as well as the subsequent reduction of the cancer-associated cytokine network may be a crucial mechanism of the antitumoral function of PSMA7 in patients with cSCC.

Immunosenescence and Skin: A State of Art of Its Etiopathogenetic Role and Crucial Watershed for Systemic Implications.

Immunosenescence is a complex multifactorial phenomenon consisting of wide-ranging remodeling of the immune system during the life span, resulting in an age-related qualitative-quantitative decline of immune cells and cytokines. A growing body of evidence in the international literature is highlighting the etiopathogenetic role of skin immunosenescence in the onset of various dermatologic conditions. Skin immunosenescence also serves as an interesting watershed for the onset of system-wide conditions in the context of allergic inflammation. Moreover, in recent years, an increasingly emerging and fascinating etiopathogenetic parallelism has been observed between some mechanisms of immunosenescence, both at cutaneous and systemic sites. This would help to explain the occurrence of apparently unconnected comorbidities. Throughout our review, we aim to shed light on emerging immunosenescent mechanisms shared between dermatologic disorders and other organ-specific diseases in the context of a more extensive discussion on the etiopathogenetic role of skin immunosenescence. A promising future perspective would be to focus on better understanding the mutual influence between skin and host immunity, as well as the influence of high inter-individual variability on immunosenescence/inflammaging. This can lead to a more comprehensive "immunobiographic" definition of each individual.

Induction of Innate and Adaptive Immune Response against Recombinant HBsAg Protein Entrapped in Docosahexaenoic Acid Nanovesicles through Biomarkers.

The present study focused on demonstrating the induction of humoral and cell-mediated immunity through the establishment of a cytokine network. We hypothesized the anti-inflammatory, pro-inflammatory, and IgE antibody levels after vaccination with lyophilized recombinant HBsAg-loaded docosahexaenoic acid nanovesicles (LRPDNV), and the efficacy compared well with standard commercial recombinant hepatitis B vaccine. The cytokine network was efficiently regulated by striking a balance between pro-inflammatory cytokines IL-6, IL-8R, and IL-12 and anti-inflammatory cytokines such as IL-2, IL-4, IL-10, and IFN-γ immune response on the 14th and 30th day after primary and booster immunization. The acute phase protein CRP level was increased due to IL-6 after immunizing with LRPDNV. On the other hand, the IgE level was not significantly increased to induce any allergic reactions after immunization with LRPDNV. The study concluded that after immunizing with LRPDNV, a significant immunological response was established, implying that DHA nanovesicles have significant potential as an adjuvant method for delivering recombinant HBsAg protein. On the other hand, following immunization with LRPDNV, the IgE level was not noticeably elevated enough to cause any adverse reactions. The study concludes that a robust immune response was developed after immunizing with LRPDNV and suggests that DHA nanovesicles have much potential to deliver recombinant HBsAg protein.

LPAR2-mediated action promotes human renal cell carcinoma via MAPK/NF-κB signaling to regulate cytokine network.

PURPOSE: Lysophosphatidic acid (LPA) exerts various physiological and pathological effects by activating its distinct G-protein-coupled LPA receptors. We demonstrated that LPA can increase the migration and proliferation of renal carcinoma cells. Meanwhile, LPAR1 and LPAR2 were preferentially expressed in renal cancer (RC) cell lines. So, the study aimed to determine the LPA receptor subtypes involved in LPA-induced actions and whether they could be used as a precision therapeutic target for renal cancer. METHODS: Biological approaches combined with big data analysis were used to demonstrate the role of LPAR2 in the progression of renal cancer. RESULTS: We found that the proliferation, clone formation, and migration in response to LPA were enhanced in LPAR2-overexpressing renal cancer cells, whereas, the actions were suppressed by LPAR2 antagonist in the cells. LPAR2 has also shown clinical diagnostic and prognostic value in renal carcinoma based on bioinformatics analysis and clinical tissue microarray analysis. In vivo study shown that tumor growth and metastasis were significantly increased in the LPAR2-overexpressing cells-derived solid tumors. LPA stimulated MAPK and NF-κB activation, and LPA-induced actions were inhibited by MAPKs and NF-κB inhibitors, respectively. Subsequently, the transcriptomic results revealed that LPAR2 strongly affected the cytokines production, and the increased IL6, CXCL8, and TNF were confirmed again using Kit assay. CONCLUSIONS: We have identified that LPAR2 is critical for LPA-promoted renal cancer progression, and the actions mainly dependent the MAPK and NF-κB activation mechanism. Then, the expression of inflammatory factors activated by NF-κB is also suspected to be involved in LPAR2-mediated carcinogenesis. Thus, LPAR2 may be a promising therapeutic target for renal cancer.

Multiplex Analysis of Serum Cytokine Profiles in Systemic Lupus Erythematosus and Multiple Sclerosis.

Changes in cytokine profiles and cytokine networks are known to be a hallmark of autoimmune diseases, including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). However, cytokine profiles research studies are usually based on the analysis of a small number of cytokines and give conflicting results. In this work, we analyzed cytokine profiles of 41 analytes in patients with SLE and MS compared with healthy donors using multiplex immunoassay. The SLE group included treated patients, while the MS patients were drug-free. Levels of 11 cytokines, IL-1b, IL-1RA, IL-6, IL-9, IL-10, IL-15, MCP-1/CCL2, Fractalkine/CX3CL1, MIP-1a/CCL3, MIP-1b/CCL4, and TNFa, were increased, but sCD40L, PDGF-AA, and MDC/CCL22 levels were decreased in SLE patients. Thus, changes in the cytokine profile in SLE have been associated with the dysregulation of interleukins, TNF superfamily members, and chemokines. In the case of MS, levels of 10 cytokines, sCD40L, CCL2, CCL3, CCL22, PDGF-AA, PDGF-AB/BB, EGF, IL-8, TGF-a, and VEGF, decreased significantly compared to the control group. Therefore, cytokine network dysregulation in MS is characterized by abnormal levels of growth factors and chemokines. Cross-disorder analysis of cytokine levels in MS and SLE showed significant differences between 22 cytokines. Protein interaction network analysis showed that all significantly altered cytokines in both SLE and MS are functionally interconnected. Thus, MS and SLE may be associated with impaired functional relationships in the cytokine network. A cytokine correlation networks analysis revealed changes in correlation clusters in SLE and MS. These data expand the understanding of abnormal regulatory interactions in cytokine profiles associated with autoimmune diseases.

Jak Inhibitors for Treatment of Autoimmune Diseases: Lessons from Systemic Sclerosis and Systemic Lupus Erythematosus.

Systemic sclerosis and systemic lupus erythematosus represent two distinct autoimmune diseases belonging to the group of connective tissue disorders. Despite the great progress in the basic science, this progress has not been translated to the development of novel therapeutic approaches that can radically change the face of these diseases. The discovery of JAK kinases, which are tyrosine kinases coupled with cytokine receptors, may open a new chapter in the treatment of so far untreatable diseases. Small synthetic compounds that can block Janus kinases and interact directly with cytokine signalling may provide therapeutic potential in these diseases. In this review, we discuss the therapeutic potential of Jak kinases in light of the cytokine network that JAK kinases are able to interact with. We also provide the theoretical background for the rationale of blocking cytokines with specific JAK inhibitors.

Resistin Associated With Cytokines and Endothelial Cell Adhesion Molecules Is Related to Worse Outcome in COVID-19.

Introduction: Resistin is reported to form a cytokine network and cause endothelial damage. The pathogenesis of coronavirus disease 2019 (COVID-19) remains unknown, but the association between cytokine storm and endothelial damage is crucial. This study aimed to evaluate resistin in COVID-19 pathogenesis compared with sepsis. Materials and Methods: First, we evaluated the association of plasma resistin levels and disease severity and clinical outcome in two large cohorts: a publicly available cohort including 306 COVID-19 patients in the United States (MGH cohort) and our original cohort including only intubated 113 patients in Japan (Osaka cohort 1). Second, to understand pathogenesis, we evaluate resistin, cytokines and endothelial cell adhesion molecules in COVID-19 compared with sepsis. Blood samples were collected from 62 ICU-treated COVID-19 patients and 38 sepsis patients on day 1 (day of ICU admission), days 2-3, days 6-8, and from 18 healthy controls (Osaka cohort 2). The plasma resistin, inflammatory cytokines (IL-6, IL-8, MCP-1 and IL-10) and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were compared between patients and control. Correlations among resistin, inflammatory cytokines and endothelial cell adhesion molecules were evaluated in COVID-19 and sepsis. Results: In the MGH cohort, the day 1 resistin levels were associated with disease severity score. The non-survivors showed significantly greater resistin levels than survivors on days 1, 4 and 8. In the Osaka cohort 1, 28-day non-survivors showed significantly higher resistin levels than 28-day survivors on days 6-8. Patients with late recovery (defined as the day of weaning off mechanical ventilation >12 or death) had significantly higher resistin levels than those with early recovery on day 1 and days 6-8. In the Osaka cohort 2, plasma resistin levels were elevated in COVID-19 and sepsis patients compared to controls at all measurement points and were associated with inflammatory cytokines and endothelial cell adhesion molecules. Conclusion: Resistin was elevated in COVID-19 patients and was associated with cytokines and endothelial cell adhesion molecules. Higher resistin levels were related to worse outcome.

Wound-healing and cytokine-modulating potential of medicinal oil formulation comprising leaf extract of Murraya koenigii and olive oil / Potencial de cicatrização de feridas e modulação de citocinas de formulação de óleo medicinal compreendendo extrato de folhas de Murraya koenigii e azeite de oliva

The study investigated the wound healing effect of medicinal oil (MO) formulation prepared from Murraya koenigii leaves extract (methanolic) incorporated in olive oil. The MO was visually transparent, homogenous, smooth in texture, the viscosity grade was observed as 140 cP and easily spreadable. Pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α were significantly reduced to 82.3 ± 3.5, 156 ± 6.2, 137.3. ± 5.5 pg/ml, respectively after treatment with MO when compared to disease control animals that showed IL-1ß, IL-6, and TNF-α levels of 170 ± 6, 265 ± 7, and 288.6 ± 11, pg/ml respectively. The level of pro-inflammatory cytokine in povidone iodine solution (PIS) group was 95.3 ± 3, 162 ± 6, 177.6 ± 8.9 pg/ml of IL-1ß, IL-6, and TNF-α respectively. Interestingly, the wound-healing efficacy of MO was found better as compared to povidone iodine treated standard group and concluded that MO has excellent wound healing effect.

O estudo investigou o efeito cicatrizante da formulação de óleo medicinal (MO) preparado a partir do extrato de folhas de Murraya koenigii (metanol) incorporado ao azeite de oliva. O MO era visualmente transparente, homogêneo, de textura lisa, o grau de viscosidade observado foi de 140 cP e facilmente espalhável. As citocinas pró-inflamatórias IL-1ß, IL-6 e TNF-α foram significativamente reduzidas para 82,3 ± 3,5, 156 ± 6,2, 137,3. ± 5,5 pg/ml, respectivamente, após o tratamento com MO quando comparados aos animais controle da doença que apresentaram níveis de IL-1ß, IL-6 e TNF-α de 170 ± 6, 265 ± 7 e 288,6 ± 11, pg/ml, respectivamente . O nível de citocina pró-inflamatória no grupo solução de iodopovidona (PIS) foi de 95,3 ± 3, 162 ± 6, 177,6 ± 8,9 pg/ml de IL-1ß, IL-6 e TNF-α, respectivamente. Curiosamente, a eficácia de cicatrização de feridas de MO foi encontrada melhor em comparação com o grupo padrão tratado com iodopovidona e concluiu que a preparação de MO tem efeito de cicatrização de feridas.

The suppression of IL-17 production from T cells by gallate-type procyanidin is mediated by selectively inhibiting cytokine production from dendritic cells.

Abnormal T helper 17 (Th17) responses promote inflammation and cause inflammatory diseases. Natural components that modulate Th17 functions can be effective for the amelioration of inflammatory diseases. Procyanidin B2 3,3''-di-O-gallate (PCB2DG) contained in grape seeds markedly suppressed interleukin (IL)-17 production from spleen cells but not CD4+ T cells. The aim of this study was to elucidate the mechanisms by which PCB2DG suppresses IL-17. Our results showed that PCB2DG suppressed the production of IL-17, tumor necrosis factor (TNF)-α, IL-1ß, and IL-6 with the suppression of transcription factors expression. In addition, we revealed that TNF-α and IL-1ß were required to induce IL-17 production in this experimental condition, and PCB2DG suppressed these cytokines from dendritic cells (DCs). Furthermore, CD4-DC co-culture experiments showed that the production of IL-17, TNF-α, and IL-1ß was markedly inhibited in co-cultures of PCB2DG-pretreated CD4+ T cells and DCs. These results suggested that PCB2DG first modulated TNF-α production by CD4+ T cells and then suppressed IL-1ß secretion from DCs, resulting in decreased IL-17 production. Thus, PCB2DG can control the cytokine network associated with Th17 cells, providing a novel mechanism underlying the immunosuppressive effects of polyphenols.

Flare-up of cytokines in rheumatoid arthritis and their role in triggering depression: Shared common function and their possible applications in treatment (Review).

Chronic illnesses are associated with an increased risk of depression and anxiety. Rheumatoid arthritis (RA) is a chronic autoimmune disease that typically causes damage to the joints. RA extensively impacts patients, both physically and psychologically. Depression is a common comorbid disorder with RA, which leads to worsened health outcomes. There are several cytokines that are active in the joints of patients with RA. Inflammatory cytokines serve important roles in the key processes in the joints, which usually cause inflammation, articular damage and other comorbidities associated with RA. The key role of inflammatory cytokines could be attributed to their interactions within signaling pathways. In RA, IL-1, and the cytokines of TNF-α, IL-6 and IL-18 are primarily involved. Furthermore, depression is hypothesized to be strongly associated with systemic inflammation, particularly with dysregulation of the cytokine network. The present review summarizes the current state of knowledge on these two diseases from the perspective of inflammation and cytokines, and emphasizes the possible bridge between them by exploring the involvement of systemic cytokines in both conditions.

Baked Bread Enhances the Immune Response and the Catabolism in the Human Body in Comparison with Steamed Bread.

It is unclear whether different processing methods change the biological functions of foods and how these functions are evaluated in the human body. Here, steamed bread and baked bread, the traditional staple foods in China and many Western countries, were made by steaming and baking, respectively, using one piece of fermented wheat dough and then consumed by 16 healthy young volunteers. By detecting 38 cytokines, 12 metabolic enzymes, glucose, lactate, and nicotinamide adenine dinucleotide (NADH) in the serum, the cytokine network and central metabolic pathway network were investigated to compare the effects of the two staple foods on immunity and metabolism. Compared with steamed bread, baked bread increased (p < 0.05) concentrations of fractalkine and macrophage-derived chemokine, decreased (p < 0.05) the concentration of interleukin-1RA, increased (p < 0.05) the expression level of phosphofructokinase, and decreased (p < 0.05) the expression level of glucose-6-phosphate dehydrogenase in the serum. Two network analyses indicated that baked bread, as compared to the steamed bread, enhanced communication between immune cells, increased catabolism, and decreased anabolism. Further, a correlation analysis of cytokines and metabolic enzymes suggested that the two staple foods may affect metabolism by regulating the secretion of cytokines. These findings highlight how the same raw food material processed by different methods may have different impacts on immunity and metabolism in humans.

Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage.

BACKGROUND: Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions. METHODS: Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods (< 24 h, 24-48 h, 3-5 days, and 6-8 days after SAH) and concentration levels of 41 cytokines were measured by multiplex immunoassay. Logistic regression analysis was used to identify cytokines associated with DCI and poor functional outcomes. Correlation networks were constructed to identify cytokine clusters. RESULTS: Of the 60 patients enrolled in the study, 14 (23.3%) developed DCI and 16 (26.7%) had poor functional outcomes at 3 months. DCI was associated with increased levels of PDGF-ABBB and CCL5 and decreased levels of IP-10 and MIP-1α. Poor functional outcome was associated with increased levels of IL-6 and MCP-1α. Network analysis identified distinct cytokine clusters associated with DCI and functional outcomes. CONCLUSIONS: Serum cytokine patterns in early SAH are associated with poor functional outcomes and DCI. The significant cytokines primarily modulate the inflammatory response. This supports earlier SAH studies linking inflammation and poor outcomes. In particular, this study identifies novel cytokine patterns over time that may indicate impending DCI.

Effects of exercise on inflammation in patients receiving chemotherapy: a nationwide NCORP randomized clinical trial.

PURPOSE: A growing body of research suggests that inflammation plays a role in many chemotherapy-related toxicities such as fatigue, anxiety, and neuropathy. Regular exercise can change levels of individual cytokines (e.g., reducing IL-6, increasing IL-10); however, it is not known whether exercise during chemotherapy affects relationships between cytokines (i.e., whether cytokine concentrations change collectively vs. independently). This study assessed how 6 weeks of exercise during chemotherapy affected relationships between changes in concentrations of several cytokines. METHODS: This is a secondary analysis of a randomized trial studying 6 weeks of moderate-intensity walking and resistance exercise during chemotherapy compared with chemotherapy alone. At pre- and post-intervention, patients provided blood to assess serum concentrations of cytokines IL-1ß, IL-6, IL-8, IL-10, and IFN-γ, and receptor sTNFR1. We investigated relationships between cytokines using the correlations between changes in cytokine concentrations from pre- to post-intervention. RESULTS: We obtained complete data from 293 patients (149 randomized to exercise). Exercise strengthened the correlation between concentration changes of IL-10 and IL-6 (r = 0.44 in exercisers vs. 0.11 in controls; p = 0.001). We observed the same pattern for IL-10:IL-1ß and IL-10:sTNFR1. Exercise also induced an anti-inflammatory cytokine profile, per reductions in pro-inflammatory IFN-γ (p = 0.044) and perhaps IL-1ß (p = 0.099, trend-level significance). CONCLUSIONS: Our hypothesis-generating work suggests that regular exercise during 6 weeks of chemotherapy may cause certain cytokine concentrations to change collectively (not independently). This work enhances our understanding of relationships between cytokines and complements traditional analyses of cytokines in isolation. Future work should test for replication and relationships to patient outcomes. TRIAL REGISTRATION: Clinical Trials.gov, # NCT00924651, http://www.clinicaltrials.gov .

Cytokine production pattern of T lymphocytes in neonatal arterial ischemic stroke during the first month of life-a case study.

BACKGROUND: The perinatal period carries the highest risk for stroke in childhood; however, the pathophysiology is poorly understood and preventive, prognostic, and therapeutic strategies are not available. A new pathophysiological model describes the development of neonatal arterial ischemic stroke (NAIS) as the combined result of prenatal inflammation and hypoxic-ischemic insult. Neuroinflammation and a systemic inflammatory response are also important features of NAIS. Identifying key players of the inflammatory system is in the limelight of current research. CASE PRESENTATION: We present four NAIS cases, in whom detailed analysis of intracellular and plasma cytokine levels are available from the first month of life. All neonates were admitted with the initial diagnosis of hypoxic ischemic encephalopathy (HIE); however, early MRI examination revealed NAIS. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Peripheral blood mononuclear cells were assessed with flow cytometry and plasma cytokine levels were measured. Pooled data from the cohort of four NAIS patients were compared to infants with HIE. At 6 and 72 h of age, the prevalence of IL10+ CD8+ lymphocytes remained lower in NAIS. At 6 h, CD8+ lymphocytes in NAIS produced more IL-17. At 72 h, CD8+ cells produced more IL-6 in severe HIE than in NAIS, but IL-6 production remained elevated in CD8 cells at 1 month in NAIS, while it decreased in HIE. At 1 week, the prevalence of TGF-ß + lymphocytes prone to enter the CNS was elevated in NAIS. On the other hand, by 1 month of age, the prevalence of TGF-ß + CD4+ lymphocytes decreased in NAIS compared to HIE. At 72 h, we found elevated plasma levels of IL-5, MCP-1, and IL-17 in NAIS. By 1 month, plasma levels of IL-4, IL-12, and IL-17 decreased in NAIS but remained elevated in HIE. CONCLUSIONS: Differences in the cytokine network are present between NAIS and HIE. CD8 lymphocytes appear to shift towards the pro-inflammatory direction in NAIS. The inflammatory response appears to be more pronounced at 72 h in NAIS but decreases faster, reaching lower plasma levels of inflammatory markers at 1 month.

How to Monitor the Neuroimmune Biological Response in Patients Affected by Immune Alteration-Related Systemic Diseases.

The clinical management of patients affected by systemic diseases, including cancer and autoimmune diseases, is generally founded on the evaluation of the only markers related to the single disease rather than the biological immuno-inflammatory response of patients, despite the fundamental role of cytokine network in the pathogenesis of cancer and autoimmunity is well known. Cancer progression has appeared to be associated with a progressive decline in the blood levels of the main antitumor cytokines, including IL-2 and IL-12, in association with an increase in those of inflammatory cytokines, including IL-6, TNF-alpha, and IL-1-beta, and immunosuppressive cytokines, namely TGF-beta and IL-10. On the other hand, the severity of the autoimmune diseases has been proven to be greater in the presence of high blood levels of IL-17, TNF-alpha, IL-6, IL-1-beta, IFN-gamma, and IL-18, in association with low levels of TGF-beta and IL-10. However, because of excessive cost and complexity of analyzing the data regarding the secretion of the single cytokines, the relation between lymphocyte-induced immune activation and monocyte-macrophage-mediated immunosuppression has been recently proven to be expressed by the simple lymphocyte-to-monocyte ratio (LMR). The evidence of low LMR values has appeared to correlate with a poor prognosis in cancer and with a disease control in the autoimmune diseases. Moreover, since the in vivo immunoinflammatory response is physiologically under a neuroendocrine modulation, for the evaluation of patient biological response it would be necessary to investigate the function of at least the two main neuroendocrine structures involved in the neuroendocrine modulation of the immune responses, consisting of the hypothalamic-pituitary-adrenal axis and the pineal gland, since the lack of physiological circadian rhythm of cortisol and pineal hormone melatonin has appeared to be associated with a worse prognosis in the human systemic diseases.

Hierarchical, imbalanced pro-inflammatory cytokine networks govern the pathogenesis of chronic arthropathies.

BACKGROUND: Chronic inflammatory arthropathies, such as rheumatoid arthritis (RA), spondyloarthritis, including psoriatic arthritis (PsA), ankylosing spondyloarthritis (AS), osteoarthritis (OA), and intervertebral disc degenerative disease (DDD) constitute major public health problems that are anticipated to grow significantly as the human population ages. However, many aspects concerning the molecular mechanisms underlying their onset and progression remain unclear. DESIGN: This narrative review critically analyzes the molecular mechanisms underlying the inflammation-associated pathogenesis of the aforementioned joint diseases. This includes, in particular, the major role played by several key soluble factors (such as cytokines and the associated signaling pathways, designated as "fragile nodes") produced by local cells and recruited to the joints' immune cells, whose elimination by specific drugs has dramatically improved the diseases' symptomatology and outcome in human clinical trials or in rodent arthritis models. HYPOTHESIS AND THE AIM OF THIS REVIEW: We hypothesize that the pathogenesis of chronic inflammatory arthropathies is governed by hierarchical, imbalanced pro-inflammatory cytokine networks (HIPICNs) (comprising a combination of fragile nodes) that are created during the development of both autoimmune (RA, PsA, and AS) and non-autoimmune (OA and DDD) disorders. The main aim of this review is to provide evidence that despite substantial pathobiological differences between these arthropathies, the HIPICNs created are quite common, thus justifying the merging of these disorders mechanistically and suggesting that these common mechanisms exist in the onset and progression of different joint diseases.

Distinct cytokine patterns may regulate the severity of neonatal asphyxia-an observational study.

BACKGROUND: Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels in moderate and severe asphyxia in order to identify players of the inflammatory response that may influence patient outcome. METHODS: We analyzed the data of 28 term neonates requiring moderate systemic hypothermia in a single-center observational study. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Neonates were divided into a moderate (n = 17) and a severe (n = 11) group based on neuroradiological and amplitude-integrated EEG characteristics. Peripheral blood mononuclear cells were assessed with flow cytometry. Cytokine plasma levels were measured using Bioplex immunoassays. Components of the kynurenine pathway were assessed by high-performance liquid chromatography. RESULTS: The prevalence and extravasation of IL-1b + CD4 cells were higher in severe than in moderate asphyxia at 6 h. Based on Receiver operator curve analysis, the assessment of the prevalence of CD4+ IL-1ß+ and CD4+ IL-1ß+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia. Intracellular levels of TNF-α in CD4 cells were increased at all time points compared to 6 h in both groups. At 1 month, intracellular levels of TNF-α were higher in the severe group. Plasma IL-6 levels were higher at 1 week in the severe group and decreased by 1 month in the moderate group. Intracellular levels of IL-6 peaked at 24 h in both groups. Intracellular TGF-ß levels were increased from 24 h onwards in the moderate group. CONCLUSIONS: IL-1ß and IL-6 appear to play a key role in the early events of the inflammatory response, while TNF-α seems to be responsible for prolonged neuroinflammation, potentially contributing to a worse outcome. The assessment of the prevalence of CD4+ IL-1ß+ and CD4+ IL-1ß+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia.

Effect of resistant and digestible rice starches on human cytokine and lactate metabolic networks in serum.

Resistant starch generated after treating ordinary starch is of great significance to human health in the countries with overnutrition. However, its functional evaluation in the human body has been rarely reported. By determining the lactate metabolic flux, 12 serum enzymes expression level and 38 serum cytokines in healthy volunteers, the variation in cytokine network and lactate metabolic network in serum were investigated to compare the mechanism of the physiological effects between the two starches. The results indicated that compared with digestible starch, resistant starch had anti-inflammatory effects, increased anabolism, and decreased catabolism. Further, the intercellular communication networks including cytokine and lactate metabolic networks were mapped out. The relationship suggested that resistant starch might affect and control the secretion of cytokines to regulate lactate metabolic network in the body, promoting the development of immunometabolism.

Changes in cytokine and chemokine expression distinguish dysthymic disorder from major depression and healthy controls.

An important area of uncertainty is the inflammatory degree to which depression occurring as part of dysthymic disorder may differ from major depression. Using a 27-plex cytokine assay, we analyzed the serum of 12 patients with dysthymic disorder, 12 with major depression, and an age-, sex-, and body mass index-matched control group of 20 healthy volunteers. We observed that patients with dysthymic disorder exhibited aberrant cytokine and chemokine expression compared with healthy controls and patients with major depression. The levels of interferon-γ-induced protein 10 highly predicted dysthymic disorder. Network analyses revealed that in patients with dysthymic disorder, the vertices were more sparsely connected and adopted a more hub-like architecture, and the connections from neighboring vertices of interleukin 2 and eotaxin-1 increased. After treatment with the same antidepressant, there was no difference between dysthymic disorder and major depression regarding any of the cytokines or chemokines analyzed. For dysthymic disorder, changes in the levels of interferon-γ-induced protein 10 and macrophage inflammatory protein-1α correlated with depression improvement. The findings suggest that the cytokine milieu in dysthymic disorder differs either at the level of individual expression or in network patterns. Moreover, chemokines play an important role in driving the pathophysiology of dysthymic disorder.