scholarly journals Safety and Pharmacokinetics of Intravesical Chitosan/Interleukin-12 Immunotherapy in Murine Bladders

2021 ◽  
pp. 1-11
Author(s):  
Khue G. Nguyen ◽  
Ethan S. Wagner ◽  
Maura R. Vrabel ◽  
Siena M. Mantooth ◽  
Danielle M. Meritet ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Responses ◽  
Acute Inflammation ◽  
Inflammatory Responses ◽  
Interleukin 12 ◽  
Laboratory Mice ◽  
Serum Cytokine ◽  
Preclinical Models ◽  
Intravesical Administration ◽  
Cytokine Levels

BACKGROUND: Intravesical administration of interleukin 12 (IL-12) co-formulated with the biopolymer, chitosan (CS/IL-12), has demonstrated remarkable antitumor activity against preclinical models of bladder cancer. However, given historical concerns regarding severe toxicities associated with systemic IL-12 administration in clinical trials, it is important to evaluate the safety of intravesical CS/IL-12 prior to clinical translation. OBJECTIVE: To evaluate the pharmacokinetics as well as the local and systemic toxicities of intravesical CS/IL-12 immunotherapy in laboratory mice. METHODS: Local inflammatory responses in mouse bladders treated with intravesical IL-12 or CS/IL-12 were assessed via histopathology. Serum cytokine levels following intravesical and subcutaneous (s.c.) administrations of IL-12 or CS/IL-12 in laboratory mice were compared. Systemic toxicities were evaluated via body weight and liver enzyme levels. RESULTS: Intravesical IL-12 and CS/IL-12 treatments did not induce significant local or systemic toxicity. IL-12 dissemination and exposure from intravesical administration was significantly lower compared to s.c. injections. Weekly intravesical CS/IL-12 treatments were well-tolerated and did not result in blunted immune responses. CONCLUSIONS: Intravesical CS/IL-12 is safe and well-tolerated in mice. In particular, the lack of cystitis and acute inflammation justifies continued investigation of intravesical CS/IL-12 immunotherapy in larger animals and patients with bladder cancer.

Circuit resistance training in sedentary women: body composition and serum cytokine levels

2010 ◽  
Vol 35 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Fabiano Candido Ferreira ◽  
Alexandra Ivo de Medeiros ◽  
Cristiane Nicioli ◽  
João Elias Dias Nunes ◽  
Gilberto Eiji Shiguemoto ◽  
...  
Keyword(s):  
Body Composition ◽  
Resistance Training ◽  
Body Mass ◽  
Inflammatory Responses ◽  
Normal Body Mass Index ◽  
Serum Cytokine ◽  
Cytokine Levels ◽  
Circuit Resistance Training ◽  
Sedentary Women ◽  
Circuit Resistance

Exercise can generate alterations in body composition and modulate the immune system. The objective of this study was to verify whether a circuit resistance training (CRT) protocol can increase lean body mass (LM), and reduce fat body mass (FM) and the percent of FM (%FM) of sedentary women, without inducing inflammatory responses, indicated by serum cytokine levels. The initial hypothesis was that CRT would improve body composition, without changing serum cytokine levels. The study consisted of 14 healthy, sedentary women, aged 33–45 years (mean ± SD, 40.23 ± 3.98 years), with a normal body mass index. They participated in 3 sessions per week of CRT, which included 2 rounds in 9 stations with 1 set of 8–12 repetition maximum at each station, for 10 weeks. During the 10-week CRT period, participants maintained their pretraining nutritional standard. Body composition was analysed with dual-energy X-ray absorptiometry both pre- and post-training. Blood samples were collected after 96 h of rest pre- and post-training, and 5 min, 24 h, and 48 h after the second and last training sessions to measure serum cytokine levels by flow cytometry. The nutritional standard was accompanied throughout the study period with 24-h dietary recall. Increases in LM (35.937 ± 4.926 to 39.130 ± 4.950 kg) and decreases in FM (21.911 ± 8.150 to 17.824 ± 4.235 kg) and %FM (37.10 ± 10.84 to 31.19 ± 6.06), without concurrent changes in serum cytokine levels, and in the nutritional standard (α = 0.05). The proposed CRT improved body composition and did not induce any changes in serum cytokine levels characteristic of the inflammatory response in women.

scholarly journals An observational study of innate immune responses in patients with acute appendicitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Toon Peeters ◽  
Sandrina Martens ◽  
Valentino D’Onofrio ◽  
Mark H. T. Stappers ◽  
Jeroen C. H. van der Hilst ◽  
...  
Keyword(s):  
Acute Appendicitis ◽  
Immune Responses ◽  
Complicated Appendicitis ◽  
Healthy Controls ◽  
Innate Immune Responses ◽  
Serum Cytokine ◽  
Post Surgery ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Recognition Receptor

Abstract Acute appendicitis is a common surgical emergency worldwide. Exaggerated immune responses could be associated with appendicitis. This study aimed at characterizing immune responses towards a large variety of gut commensals and pathogens, and pattern recognition receptor (PRR) ligands, and investigating the course of systemic inflammation in a prospective cohort of acute appendicitis patients. PBMC responses of 23 patients of the cohort and 23 healthy controls were characterized more than 8 months post-surgery. Serum cytokine levels were measured in 23 patients at the time of appendicitis and after one month. CRP, WBC and percentage of neutrophils were analyzed in the total cohort of 325 patients. No differences in PBMC responses were found between patients and controls. Stronger IL-10 responses were found following complicated appendicitis. A trend towards lower IL-8 responses was shown following gangrenous appendicitis. Serum IL-10 and IL-6 were significantly elevated at presentation, and IL-6, IL-8 and TNF-α levels were higher in complicated appendicitis. Routine biomarkers could predict severity of appendicitis with high specificities, but low sensitivities. Cytokine responses in patients following acute appendicitis did not differ from healthy controls. Higher serum cytokine levels were found in acute complicated and gangrenous cases. Further research into discriminative biomarkers is warranted.

scholarly journals Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent but clinically inapparent in cancer patients under immune checkpoint therapy

2021 ◽  
Author(s):  
Thomas Walle ◽  
Sunanjay Bajaj ◽  
Joscha A. Kraske ◽  
Thomas Rösner ◽  
Christiane S. Cussigh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Elevated Serum ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Serum Cytokine ◽  
Short Term ◽  
Cytokine Levels ◽  
Tumor Types

AbstractCancer patients frequently receive immune checkpoint therapies (ICT) which may modulate immune responses to COVID-19 vaccines. Recently, cytokine release syndrome (CRS) was observed in a cancer patient who received the BTN162b2 vaccine under ICT. Here, we analyzed adverse events (AEs) in patients of various solid tumor types undergoing (n=64) or not undergoing (n=26) COVID-19 vaccination under ICT as an exploratory endpoint of a prospectively planned cohort study. We did not observe clinically relevant CRS after vaccination (95% CI [0,0.056]). Short term (<4 weeks) serious AEs were rare (12.5%) and overall AEs under ICT were comparable to unvaccinated patients. Despite the absence of CRS symptoms, we observed a pairwise-correlated set of CRS-associated cytokines upregulated in 42% of patients after vaccination and ICT (>1.5fold). Hence, clinically meaningful CRS appears to be rare in cancer patients under ICT and elevated serum cytokine levels are common but not sufficient to establish CRS diagnosis.

scholarly journals Serum cytokine profiles in healthy nonhuman primates are blunted by sedation and demonstrate sexual dimorphism as detected by a validated multiplex immunoassay

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Hocum Stone ◽  
Scott Hunter Oppler ◽  
Julia L. Nugent ◽  
Sarah Gresch ◽  
Bernhard J. Hering ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Clinical Settings ◽  
Model Design ◽  
Serum Cytokine ◽  
Serum Cytokines ◽  
Cytokine Levels ◽  
The Impact ◽  
Cytokine Profiling

AbstractCytokine profiling is a valuable tool for monitoring immune responses associated with disease and treatment. This study assessed the impact of sex and sedation on serum cytokines in healthy nonhuman primates (NHPs). Twenty-three cytokines were measured from serum using a bead-based multiplex assay. Assay validation for precision, sensitivity, recovery, linearity, and stability was performed. Samples from male and female cynomolgus and rhesus macaques either cooperating or sedated were compared. All cytokines except TNFα demonstrated acceptable sensitivity and precision, with variable recovery and linearity. IFNγ, IL-2, IL-5, IL-6, IL-8, IL-12/23 (p40), IL-13, IL-15, MCP-1, TGFα, VEGF met acceptance criteria; G-CSF, IL-4, IL-10, MIP1α, sCD40L were marginal. Higher cytokine levels were observed in females and cytokine levels were blunted in sedated NHPs when compared to awake cooperating NHPs. Significant differences observed in cytokines related to sex, species, or imposed by handling highlight the importance of model design on translational relevance for clinical settings.

622: Intravesical Interleukin-12 Gene Therapy in an Orthotopic Bladder Cancer Model

2006 ◽  
Vol 175 (4S) ◽  
pp. 200-201
Author(s):  
Minoru Horinaga ◽  
Kelley Harsch ◽  
Ryuichi Fukuyama ◽  
Warren Heston ◽  
William Larchian
Keyword(s):  
Gene Therapy ◽  
Bladder Cancer ◽  
Interleukin 12 ◽  
Cancer Model ◽  
Bladder Cancer Model

An Examination of Generalized Pustular Psoriasis in Pregnancy Based on the Serum Cytokine Levels.

1999 ◽  
Vol 61 (2) ◽  
pp. 144-147
Author(s):  
Miyako KUDO ◽  
Yoshihiro UMEBAYASHI ◽  
Tomoe KOTSUJI ◽  
Fujio OTSUKA
Keyword(s):  
Pustular Psoriasis ◽  
Serum Cytokine ◽  
Cytokine Levels ◽  
Generalized Pustular Psoriasis ◽  
In Pregnancy

THE EFFECT OF SUBACUTE INTOXICATION WITH ETHYLENE CHLOROHYDRIN ON IMMUNE RESPONSES, TH1 AND TH2 LYMPHOCYTE FUNCTION AND CYTOKINE LEVELS IN RATS BLOOD

2017 ◽  
pp. 27-30
Author(s):  
P. F. Zabrodskii ◽  
V. V. Maslyakov ◽  
M. S. Gromov
Keyword(s):  
Immune Responses ◽  
Inflammatory Cytokine ◽  
Albino Rats ◽  
Lymphocyte Function ◽  
Ethylene Chlorohydrin ◽  
Immunoregulatory Cytokines ◽  
Cytokine Levels ◽  
Th1 And Th2 Lymphocytes ◽  
Cellular Immune ◽  
Th1 And Th2

In experiments on outbred albino rats, it was established that subacute intoxication with ethylene chlorohydrin (0.2 LD50 daily for 4 days) causes a decrease in Th1 and Th2 lymphocytes function to the same extent, diminishes parameters of humoral and cellular immune responses and the content of immunoregulatory cytokines IFN- , IL-2, IL-4 in blood, increases concentrations of pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10.

scholarly journals Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eunyoung Emily Lee ◽  
Kyoung-Ho Song ◽  
Woochang Hwang ◽  
Sin Young Ham ◽  
Hyeonju Jeong ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Clustering Analysis ◽  
Validation Cohort ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Severe Disease ◽  
Outcome Data ◽  
Inflammatory Immune Response ◽  
Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

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