Cytokine Pattern Research Articles

Soluble CD163 Identifies Those at Risk for Increased Hepatic Inflammation & Fibrosis.

BackgroundLiver disease remains a significant cause of morbidity and mortality in HIV-infected persons. Soluble CD163 is a marker of Kupffer cell activation that is highly associated with development of hepatic fibrosis. The relative contributions of HIV-associated systemic immune activation vs other etiologies of injury are poorly characterized.MethodsWe utilized subjects in the Miami Adult Studies on HIV (MASH) cohort to evaluate 464 participants including 361 people with HIV (PWH) and 103 hepatitis C virus (HCV)/HIV-uninfected controls. Subjects underwent testing for hepatic fibrosis using both magnetic resonance elastography and the Enhanced Liver Fibrosis Index. Steatosis was evaluated by magnetic resonance imaging–derived proton density fat fraction. Immune activation markers and cytokines were quantitated using Luminex methodologies.ResultsParticipants with HIV with or without HCV coinfection had higher levels of sCD163 than uninfected controls (P < .05). Soluble sCD163 was highly associated with elevated alanine aminotransferase, a key marker of inflammation/injury and with hepatic fibrosis. Hepatic steatosis was also associated with a cytokine pattern suggestive of Kupffer cell activation but was not associated with an increase in sCD14 or sCD27.ConclusionsInjury and resultant hepatic fibrosis occur by distinct though overlapping mechanistic pathways. In PWH, sCD163 is highly associated with both injury and fibrosis, suggesting that persistent systemic immune activation is a major contributor to long-term outcomes, adding to damage caused by alcohol, steatosis, and other hepatotoxic drug effects.

Co-existence of specific IgE antibodies and T cells reactive to house dust mites and human transglutaminase3/tropomysin in patients with atopic dermatitis.

Although specific IgE antibodies reactive to exogenous antigens are found in patients with atopic dermatitis (AD), some patients do not have such antibodies. Autoimmunity has been proposed as a possible mechanism in these patients. To identify specific IgE antibodies reactive to human transglutaminase 3 (TG3) and tropomysin (TMP) and determine whether auto-reactive T cells are induced by these proteins in patients with AD. Forty-two patients with AD and 27 healthy controls were included in this study. IgE antibodies against recombinant human TG3 and TMP were measured by ELISA. Cross-reactivity between allergens was determined by EdU of peripheral blood mononuclear cells (PBMCs) proliferation assays. T-cell lines were generated from PBMCs in the presence of house dust mites (HDM), TG3 and TMP. TG3/TP-specific T-cell clones were generated from T-cell lines, and were characterized by antigen specificity and cytokine pattern. In 12 patients with anti-HDM IgE antibodies, six (50%) had anti-TG3 IgE antibody and four (33.3%) had both anti-TG3 and anti-TMP IgE antibodies. Lymphocyte proliferation was induced in 12 patients by TG3 or TMP. T-cell lines and T-cell clones from PBMCs of patients with AD who had IgE antibody reactive to HDM were fully cross-reactive with TG3 and TMP. These cell clones included both Th1 cell (producing IFN-γ) and Th2 cell (inducing IL-4) responses. TG3-and TMP-specific T-cell clones were not generated from healthy controls. Specific IgE antibody and T cell clones reactive to human TG3 and TMP were found in patients with AD, indicating that an autoimmune mechanism might contribute to AD.

Shared microbiological and immunological patterns in periodontitis and IBD: A scoping review

ObjectivesTo extract the microbiological and immunological evidence underpinning the association between periodontitis and inflammatory bowel disease (IBD).MethodsRelevant articles were sorted through a systematic search on PubMed, Embase, Scopus and Web of Science up to October 2020. Available evidence was grouped in three different clusters: (a) studies that examined oral microbial alterations in IBD patients; (b) studies that investigated intestinal dysbiosis in patients with periodontitis; and (c) evidence for a shared immunological pattern between the two conditions.ResultsA total of 15 studies involving 1,171 patients were included. Oral microbiome, either subgingival or salivary, was consistently altered in patients with IBD compared to healthy subjects (a) Additionally, gut dysbiotic microbiota of IBD patients was colonized by pathobionts from oral origin, either via haematogenous or enteric route. Suffering from periodontitis is associated with lower alpha diversity in the gut microbiome (b) Lastly, both IBD and periodontitis are characterized by similar expression patterns of inflammatory cytokines at the gingival and gut levels that are exacerbated when both diseases are present (c).ConclusionsPeriodontitis and IBD share common dysbiotic and immunological traits. Well‐designed preclinical models and longitudinal cohort studies are required to better explore the causal pathways between the two conditions (PROSPERO CRD42020194379).

Heart-Associated Cytokine and Endothelial Patterns Dominate the Ischemia/Reperfusion Response in Recipients of Combined Heart/Lung Transplantation in Comparison to Lung Transplantation

Heart-Associated Cytokine and Endothelial Patterns Dominate the Ischemia/Reperfusion Response in Recipients of Combined Heart/Lung Transplantation in Comparison to Lung Transplantation

Serum Concentration of Inflammatory Cytokines in Dogs with Suspected Acute Pancreatitis.

Acute pancreatitis is an acute inflammatory process in the pancreas that is common in dogs. This study was designed to compare cytokines between healthy dogs and dogs with suspected acute pancreatitis. For the canine cytokine antibody array, three healthy dogs and three dogs with suspected acute pancreatitis were included. Interleukin (IL)-2, IL-6, IL-10, GM-CSF, and TNF-α were not detected in either group based on the results. Conversely, IL-8 (p = 0.035), Monocyte Chemoattractant Protein-1 (MCP)-1 (p = 0.0138), Receptor for Advanced Glycation Endproducts (RAGE) (p = 0.0079), and stem cell factor (SCF) (p = 0.034) were significantly increased in dogs with suspected acute pancreatitis. However, vascular endothelial growth factor (VEGF) (p = 0.6971) did not differ significantly between groups. For the canine serum Enzyme-Linked Immunosorbent Assay (ELISA), eight healthy dogs and eight dogs with suspected acute pancreatitis were included. ELISA revealed that IL-8 (p < 0.0001), MCP-1 (p < 0.0001), RAGE (p = 0.006), and SCF (p = 0.0002) were all significantly upregulated in the experimental group. We confirmed multiple patterns of cytokines in suspected acute pancreatitis of dogs via canine cytokine antibody array using a small quantity of serum. After this procedure, we reevaluated the cytokines, which were significantly increased in dogs with suspected acute pancreatitis, by ELISA, with more samples. Through this study, we confirmed that MCP-1, RAGE, and SCF were newly suggested factors in dogs with suspected acute pancreatitis.

Glyceraldehyde-3-phosphate Dehydrogenase Common Peptides of Listeria monocytogenes, Mycobacterium marinum and Streptococcus pneumoniae as Universal Vaccines.

Universal vaccines can be prepared with antigens common to different pathogens. In this regard, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a common virulence factor among pathogenic bacteria of the genera Listeria, Mycobacterium and Streptococcus. Their N-terminal 22 amino acid peptides, GAPDH-L1 (Listeria), GAPDH-M1 (Mycobacterium) and GAPDH-S1 (Streptococcus), share 95–98.55% sequence homology, biochemical and MHC binding abilities and, therefore, are good candidates for universal vaccine designs. Here, we used dendritic cells (DC) as vaccine platforms to test GAPDH epitopes that conferred protection against Listeria monocytogenes, Mycobacterium marinum or Streptococcus pneumoniae in our search of epitopes for universal vaccines. DC loaded with GAPDH-L1, GAPDH-M1 or GAPDH-S1 peptides show high immunogenicity measured by the cellular DTH responses in mice, lacked toxicity and were capable of cross-protection immunity against mice infections with each one of the pathogens. Vaccine efficiency correlated with high titers of anti-GAPDH-L1 antibodies in sera of vaccinated mice, a Th1 cytokine pattern and high frequencies of GAPDH-L1-specific CD4+ and CD8+ T cells and IFN-γ producers in the spleens. We concluded that GAPDH-L1 peptide was the best epitope for universal vaccines in the Listeria, Mycobacterium or Streptococcus taxonomic groups, whose pathogenic strains caused relevant morbidities in adults and especially in the elderly.

Albumin Urinary Excretion Is Associated with Increased Levels of Urinary Chemokines, Cytokines, and Growth Factors Levels in Humans.

The aim of the present study was to study the associations between urine albumin excretion, and a large number of urinary chemokines, cytokines, and growth factors in a normal population. We selected 90 urine samples from individuals without CVD, diabetes, stroke or kidney disease belonging to the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females, all aged 75 years). Urinary cytokine levels were analyzed with two multiplex assays (proximity extension assays) and the cytokine levels were correlated with urine albumin. After adjustment for sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), smoking and multiplicity testing, 11 biomarkers remained significantly associated with urine albumin: thrombospondin 2, interleukin 6, interleukin 8, hepatocyte growth factor, matrix metalloproteinase-12 (MMP-12), C-X-C motif chemokine 9, tumor necrosis factor receptor superfamily member 11B, osteoprotegerin, growth-regulated alpha protein, C-X-C motif chemokine 6, oncostatin-M (OSM) and fatty acid-binding protein, intestinal, despite large differences in molecular weights. In this study, we found associations between urinary albumin and both small and large urine proteins. Additional studies are warranted to identify cytokine patterns and potential progression markers in various renal diseases.

Night shift schedule alters endogenous regulation of circulating cytokines

Night shift work is a risk factor for viral infection, suggesting that night shift schedules compromise host defense mechanisms. Prior studies have investigated changes in the temporal profiles of circulating cytokines important for priming and restraining the immune response to infectious challenges from night shift work, but not by way of a 24-h constant routine of continuous wakefulness devoid of behavioral or environmental influences. Hence the true endogenous pattern of cytokines, and the combined effect of sleep loss and circadian misalignment on these cytokines remains unknown. Here, 14 healthy young men and women underwent three days of either a simulated night shift or a simulated day shift schedule under dim light in a controlled in-laboratory environment. This was followed by a 24-h constant routine protocol during which venous blood was collected at 3-h intervals. Those who had been in the night shift schedule showed lower mean circulating TNF-α (t13 = -6.03, p < 0.001), without any significant differences in IL-1β, IL-8 and IL-10, compared with those who had been in the day shift (i.e., control) schedule. Furthermore, circulating IL-6 increased with time awake in both shift work conditions (t13 = 6.03, p < 0.001), such that temporal changes in IL-6 were markedly shifted relative to circadian clock time in the night shift condition. These results indicate that night shift work compromises host defense by creating cytokine conditions that initially impede anti-viral immunity (lower TNF-α) and may eventually promote autoimmunity (mistimed rise in IL-6).

Tender Coconut Water Protects Mice From Ischemia-Reperfusion-Mediated Liver Injury and Secondary Lung Injury.

Organ injury by oxidative and inflammatory mediators occurs during ischemia-reperfusion (I/R) of the liver. Remote organ injury secondary to liver I/R increases the systemic insult. Tender coconut water (TCW) has been studied in chemical and fructose-induced liver injury but its ability to decrease tissue injury in clinically relevant injury models is unknown. We evaluated the therapeutic potential of TCW in preventing liver I/R injury and associated remote organ injury. Mice were fed sugar water (SUG; control) or TCW for a week and then subjected to 60 min of liver ischemia followed by reperfusion for 6 h. Plasma alanine transaminase levels, tissue damage, and mRNA levels of Nos2, Tnf, and Il6 were significantly lower in mice fed TCW prior to I/R. Plasma cytokines followed liver cytokine patterns. TCW increased mRNA levels of the anti-oxidant genes Hmox1 and Ptgs2 in the liver of mice subjected to I/R. Remote lung injury from liver I/R was also decreased by TCW feeding as evident by less neutrophil infiltration, decreased pro-inflammatory Il6, and increased anti-inflammatory Il10 mRNA levels in the lung. To examine macrophage activation as a potential mechanism, TCW pretreatment decreased the amount of nitrite produced by RAW264.7 macrophages stimulated with LPS. The levels of Nos2, Il1b, Tnf, and Il6 were decreased while Il10 and Hmox1 mRNA levels were significantly up-regulated upon LPS stimulation of TCW pretreated RAW264.7 macrophages. Collectively, our results indicate that TCW decreased hepatic I/R-mediated damage to liver and lung and suggest that decreased macrophage activation contributes to this effect.

Abstract OT-15-01: A phase II trial with safety run-in of neoadjuvant therapy with an aromatase inhibitor in combination with durvalumab (MEDI4736) in postmenopausal patients with hormone-receptor-positive (HR+) breast cancer

Abstract Background: HR+ breast cancer has a long dormancy and steady rate of recurrence over decades from initial diagnosis. It is a misconception to think that HR+ disease has good prognosis since long term PFS and OS are only a few percent better for HR+ disease compared with HR- disease over a follow up of 20 years. Neoadjuvant endocrine therapy has been shown to be equivalent to chemotherapy but less toxicity. Aromatase inhibitors have also been shown to have immunomodulatory activity. In order to improve short term and long term outcomes, we started an investigator-initiated study using anastrozole plus the anti-PD-L1 antibody durvalumab in the neoadjuvant treatment of HR+/HER2- breast cancer. Methods: This is an open label, phase II with safety run-in trial conducted at Moffitt Cancer Center. The primary objective is modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0. Secondary objectives are clinical response rate, pathologic response rate, recurrence free survival. Correlative objectives include phenotypic changes in immune cells and cytokine patterns pre-, during- and post-treatment. Inclusion criteria include postmenopausal females, ECOG 0-1, HR+ with Allred score of 6 to 8, HER2-, cT2-cT4, any N, M0, appropriate lab values, agreeing to research biopsies. Exclusion criteria include multicentric disease, bilateral disease, autoimmunity or inflammatory disease, use of immunosuppressant, known HIV, Hep B/C infection, history of TB, h/o interstitial lung disease or pneumonitis, clinically significant cardiovascular disease, mean QTcF &amp;gt; 470 ms. Patients will receive anastrozole 1 mg PO daily for 6 months concurrently with durvalumab 1500 mg IV every 4 weeks for 6 cycles, followed by definitive surgery. Results: This is a trial in progress. However, limited preliminary results will be presented. Conclusion: The combination of anastrozole and durvalumab may lead to improved mPEPI score in the short term and improved RFS in the long term. Citation Format: Hung T Khong, Dawn N Goodridge, Nazanin Khakpour, M. Catherine Lee, Christine Laronga, Avan J Armaghani, Aixa E Soyano-Muller, Hyo Han, Hatem Soliman, Ricardo Costa, Loretta Loftus, Susan J Hoover, John V Kiluk, Zena Jameel, Brian J Czerniecki. A phase II trial with safety run-in of neoadjuvant therapy with an aromatase inhibitor in combination with durvalumab (MEDI4736) in postmenopausal patients with hormone-receptor-positive (HR+) breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-15-01.

Abstract PS4-16: Symptoms of cold discomfort are reduced in breast cancer patients with a composite cytokine pattern associated with increased anti-tumor immunity

Abstract Background: In preclinical models of breast cancer (BC), chronic stress enhances tumor growth and metastasis through β-adrenergic signaling as part of the “fight or flight” stress response pathway. These effects involve norepinephrine-mediated sympathetic regulation of cancer-related immunity. In a novel discovery, adrenergic stress in tumor-bearing mouse models of BC was associated with symptoms of intense cold discomfort, reduced CD8+ T cells, and higher immunosuppressive myeloid derived suppressor cells (MDSC) and regulatory T cells. BC survivors often experience heightened sympathetic activation and anecdotally report symptoms of feeling overly cold. Based on preclinical findings, symptoms of cold discomfort reported by BC survivors are hypothesized to identify those with reduced anti-cancer immunity and increased immunosuppression. Methods: Women with incident stage I to III BC were prospectively enrolled into the Women’s Health after Breast Cancer Study prior to BC treatment at Roswell Park Comprehensive Cancer Center. Participants provided blood samples and completed a survey assessing BC risk factors at the time of diagnosis and survivorship outcomes one-year post. Symptoms of being persistently and inappropriately cold as well as the occurrence of hot flashes and sweats were assessed using a Likert scale patterned on the validated Multidimensional Assessment of Fatigue Scale. A total of 424 women who had questionnaire data and plasma samples were included in the study. A panel of 27 Th1, Th2, Th9, and Th17 cytokines were assayed using a multiplex Luminex bead-based approach. Perceived symptoms of thermal discomfort were evaluated using logistic regression over cytokine tertiles (T1, T2, T3). Principal component analysis (PCA) was used to identify clusters of cytokines associated with symptoms of thermal discomfort. Cytokine composite scores were further refined based on their role with anti-tumor or pro-tumor activity. Multivariate models were adjusted for age, race, menopausal status, body mass index, stage, estrogen receptor status, grade, and treatment received. Results: Forty-six percent (195/424) of patients reported symptoms of feeling cold while 65% (275/424) experienced hot flashes and night sweats. There were no differences in patient or tumor characteristics between women who reported feeling cold versus those who did not, with women receiving chemotherapy more likely to report feeling cold (p = 0.01). Importantly, menopausal onset occurring after BC diagnosis or receipt of hormonal therapy were not associated with symptoms of feeling cold, but as expected were associated with experiencing hot flashes indicating that feeling cold is a distinct symptom from hot flashes. Higher pre-treatment levels of IL-6 was associated with 40-55% lower risk of feeling inappropriately cold 1-year post-diagnosis (T3 vs T1: OR=0.58, 95% CI: 0.34-1.00, p=0.01). PCA analysis identified a composite cytokine score at 1-year post diagnosis, which included the Th1 cytokines IL-12p70 and TNFα, IL-9 and IL-21 as cytokines involved in Th9 antitumor immunity, and the type 3 interferon IFN-λ2/IL-28α, which are all associated with increased CD8+ T cell activity. Increased scores were associated with reduced odds of feeling cold (T3 vs T1: OR=0.42, 95% CI: 0.23-0.77, p=0.02). Hot flashes in contrast were not associated with individual cytokine levels or composite scores. Conclusions: Symptoms of cold discomfort are less likely to be reported by BC survivors with a composite cytokine pattern associated with increased anti-tumor immunity. Further research is needed to determine if this symptom is associated with increased adrenergic stress and worse BC outcomes as observed in preclinical models. Citation Format: Shipra Gandhi, Maithreyi Sarma, Kristopher Attwood, Christine B. Ambrosone, Elizabeth A. Repasky, Chi-Chen Hong. Symptoms of cold discomfort are reduced in breast cancer patients with a composite cytokine pattern associated with increased anti-tumor immunity [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-16.

Sudden Hypotension and Increased Serum Interferon-γ and Interleukin-10 Predict Early Macrophage Activation Syndrome in Patients with Systemic Juvenile Idiopathic Arthritis

To identify clinical and laboratory predictors for early macrophage activation syndrome (MAS) associated with systemic juvenile idiopathic arthritis (sJIA). This is a retrospective cohort study of 149 patients with sJIA, of whom 27 had 31 episodes of MAS. We evaluated the clinical and laboratory features of patients with sJIA and MAS and compared them with those without MAS. We focused our analysis on the overall process of MAS development, especially MAS onset. As shown in previous studies, we found a high percentage of fever, absence of arthritis, and central nervous system dysfunction at MAS onset in our study cohort. We also found that 35% of patients with MAS had hypotension although not shock, and 22.6% of patients with MAS had gastrointestinal involvement at MAS onset. Compared with patients with MAS without hypotension, patients with MAS and hypotension had greater rates of admission to the intensive care unit; presented with more arthritis, serositis, pneumonia, and gastrointestinal involvement; and had greater white blood cell and absolute neutrophil counts and serum bilirubin levels and lower serum total protein. We confirmed laboratory markers such as platelet counts, lactate dehydrogenase, and aspartate aminotransferase can help to identify early MAS and that ferritin/erythrocyte sedimentation rate ratio of approximately 20.0 had a high diagnostic sensitivity and specificity for MAS. In addition, we discovered that the combination of interferon-γ >17.1 pg/mL and interleukin-10>7.8 pg/mL appeared to be a good cytokine pattern for the recognition of MAS onset. Sudden hypotension, elevated ferritin/erythrocyte sedimentation rate ratio, and the cytokine pattern of significantly increased interferon-γ and interleukin-10 levels are important markers for early identification of MAS in addition to the traditional characteristics of sJIA-associated MAS.

Hidradenitis suppurativa – The role of interleukin-17, the aryl hydrocarbon receptor and the link to a possible fungal aetiology

Hidradenitis Suppurativa (HS) is a chronic, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. The pathophysiology of the disease remains elusive, with newer therapies targeting various aspects of the dysregulated immune system.This presents a useful opportunity to look at the cytokine profile in HS and other inflammatory conditions that share similar patterns with the aim of teasing out less considered explanations for HS pathogenesis. It has been observed that IL-17 appears to be the most common denominator linking HS with other immune mediated diseases like Crohn, ulcerative colitis, multiple sclerosis and psoriasis. Given that IL-17 plays an important role in antifungal immunity, evidenced by the cytokine pattern in fungal disease and the bulk of data citing their potential involvement in Crohn, ulcerative colitis, multiple sclerosis and psoriasis; it is fair to suggest the need to explore the role that fungi play in the setting of HS going forward.The aryl hydrocarbon receptor (ahr) is a ubiquitous and largely conserved entity that is gaining interest in inflammatory conditions such as psoriasis and atopic dermatitis. It is well known to modulate autoimmune states. Its activation by both exogenous and endogenous agents result in secretion of IL-17 by Th17 cells. One of such agents is the tryptophan metabolite 6-formylindolo [3,2–b] carbazole (FICZ)-which can be produced by microorganisms such as fungi. It will be interesting to explore its usefulness in HS pathogenesis.

Adverse effects of maternal rheumatoid arthritis during pregnancy on children.

Adverse effects of maternal rheumatoid arthritis during pregnancy on children.

Coumestrol mitigates retinal cell inflammation, apoptosis, and oxidative stress in a rat model of diabetic retinopathy via activation of SIRT1.

Diabetes-induced oxidative stress is vital in initiating neuronal damage in the diabetic retina, leading to diabetic retinopathy (DR). This study investigates the possible effects of coumestrol (CMS) on streptozotocin (STZ)-induced DR. First, we established a rat model of DR by STZ injection and a cell model involving high-glucose (HG) exposure of human retinal microvascular endothelial cells (hRMECs). We characterized the expression patterns of oxidative stress indicators, pro-inflammatory cytokines, and pro-apoptotic proteins in hRMECs. Polymerase chain reaction showed sirtuin 1 (SIRT1) to be poorly expressed in the retinal tissues of STZ-treated rats and HG-exposed hRMECs, but its expression was upregulated upon treatment with CMS treatment. Furthermore, CMS treatment attenuated the STZ-induced pathologies such as oxidative stress, inflammation, and cell apoptosis. Consistent with the in vivo results, CMS activated the expression of SIRT1, thereby inhibiting oxidative stress, inflammation, and apoptosis of HG-treated hRMECs. From these findings, we concluded that CMS ameliorated DR by inhibiting inflammation, apoptosis and oxidative stress through activation of SIRT1.

Cytokine changes during immune-related adverse events and corticosteroid treatment in melanoma patients receiving immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) often cause immune-related adverse events (irAEs), most of which are treated with corticosteroids despite evidence suggesting that corticosteroids may blunt antitumor efficacy. We sought to identify cytokine changes that correlate with irAEs and study the impact of corticosteroid treatment on cytokine levels. We analyzed expression of 34 cytokines in 52 melanoma patients who developed irAEs during therapy with ICIs. Luminex serum assay was performed at baseline, 1, 2, and 3months after starting ICI. Baseline cytokine levels and longitudinal log2 fold-change was compared with incidence and grade of irAEs. Cytokine patterns were compared between patients based on development of irAEs and steroid treatment. There were no differences in baseline cytokine levels between patients who developed grade 1-2 irAEs (N = 28) vs. grade 3-4 irAEs (N = 24). Dermatitis patients (N = 8) had significantly higher baseline Ang-1 (p = 0.006) and CD40L (p = 0.005). Pneumonitis patients (N = 4) had significantly higher baseline IL-17 (p = 0.009). Colitis patients (N = 8) had a trend toward decreased GCSF (p = 0.08). Through Spearman's correlation analysis, patients who developed irAEs without receiving corticosteroids (N = 23) exhibited harmonization of cytokine fold-change, with 0/276 pairwise comparisons demonstrating significant divergence. In contrast, corticosteroid treatment in patients with irAEs (N = 15) altered fold-change to a discordant pattern (42/276 diverged, 15.2%). This discordant cytokine pattern in patients receiving corticosteroids is similar to the cytokine pattern in patients who did not develop irAEs (N = 8) during the longitudinal profiling period (41/276, 14.9%). Baseline levels of certain cytokines correlate with specific irAEs in melanoma patients receiving ICIs. irAEs drive a concordant pattern of cytokine fold-change, which is disrupted by corticosteroid treatment.

Mesenchymal stem cell-glioblastoma interactions mediated via kinin receptors unveiled by cytometry.

Glioblastoma (GBM) is one of the most malignant and devastating brain tumors. The presence of highly therapy-resistant GBM cell subpopulations within the tumor mass, rapid invasion into brain tissues and reciprocal interactions with stromal cells in the tumor microenvironment contributes to an inevitable fatal prognosis for the patients. We highlight the most recent evidence of GBM cell crosstalk with mesenchymal stem cells (MSCs), which occurs either by direct cell-cell interactions via gap junctions and microtubules or cell fusion. MSCs and GBM paracrine interactions are commonly observed and involve cytokine signaling, regulating MSC tropism toward GBM, their intra-tumoral distribution, and immune system responses. MSC-promoted effects depending on their cytokine and receptor expression patterns are considered critical for GBM progression. MSC origin, tumor heterogeneity and plasticity may also determine the outcome of such interactions. Kinins and kinin-B1 and -B2 receptors play important roles in information flow between MSCs and GBM cells. Kinin-B1 receptor activity favors tumor migration and fusion of MSCs and GBM cells. Flow and image (tissue) cytometry are powerful tools to investigate GBM cell and MSC crosstalk and are applied to analyze and characterize several other cancer types.

Biomarkers for Early Diagnosis of Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.

Many biomarkers have been proposed for the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH) in adults, but comparative studies are lacking. We analyzed ferritin, glycosylated ferritin, soluble CD25, CD163and CD14, IL-6, IFN-γ, IL-18, IL-10, IL-1ß, IL-12p70, IL-17α, IP-10, and CXCL9 levels to differentiate HLH from sepsis in critically ill patients. Of 120 patients, HLH was confirmed for 14 patients. Among the biomarkers tested, ferritin, IL-18, and glycosylated ferritin were the most efficient parameters for early diagnosis of HLH. With a sensitivity set at 85%, ferritin, IL-18, and glycosylated ferritin were the biomarkers with the highest specificity: 84, 79, and 71% respectively. Combining IL-18 with the HScore provided a new score with an increased specificity compared to the HScore alone, 86% compared to 70% with a sensitivity set at 100%. A distinct cytokine pattern was highlighted in patients with malignancy-triggered HLH, with highly increased levels of INF-ɣ and CXCL9, compared to HLH secondary to infection. This is the largest study available to date, comparing diagnostic biomarkers for HLH on a cohort of critically ill adult patients. Serum ferritin was the most discriminating parameter for early diagnosis of secondary HLH. IL18*HScore was identified as a highly potential score.

Cytokine Pattern in Piglets in the Early Postnatal Period

Cytokine Pattern in Piglets in the Early Postnatal Period

Physical Exercise and Immune System: Perspectives on the COVID-19 pandemic.

Physical exercise training (PET) has been considered an excellent non-pharmacological strategy to prevent and treat several diseases. There are various benefits offered by PET, especially on the immune system, promoting changes in the morphology and function of cells, inducing changes in the expression pattern of pro and anti-inflammatory cytokines. However, these changes depend on the type, volume and intensity of PET and whether it is being evaluated acutely or chronically. In this context, PET can be a tool to improve the immune system and fight various infections. However, the current COVID-19 pandemic, caused by SARS-CoV-2, which produces cytokine storm, inducing inflammation in several organs, with high infection rates in both sedentary and physically active individuals, the role of PET on immune cells has not yet been elucidated. Thus, this review focused on the role of PET on immune system cells and the possible effects of PET-induced adaptive responses on SARS-CoV-2 infection and COVID-19.