Cytokines and Sickness Behavior
Alan J. Husband in Psychoimmunology CNS-Immune Interactions, 2019
This chapter discusses the evidence favoring the view that cytokines act as communication signals to coordinate the many different components of the febrile response to pathogens, and especially the behavioral adjustments that are characteristic of sickness. Cytokines act in a paracrine fashion, in the local environment to stimulate immune responses, but also in an endocrine-like manner on distant targets, to mediate many of the metabolic and physiologic components of the acute phase response. Behaviorists are not used to study behavior of sick animals and pathologists are rarely interested in the behavior of sick animals. This explains why there is no standard way of assessing sickness behavior in an objective way in animals. The possibility that the defensive response to infection and inflammation is organized at different levels of regulation in the organism has turned out to be heuristically fruitful both in terms of adaptation and homeostasis and in terms of mechanisms.
The Role of Epigenetics
Dr. Ather Muneer in Mood Disorders, 2018
Mood disorders are highly heterogeneous conditions whose phenotypic expression is dependent on a complex interplay of genes and environment. In both animal and human studies a number of candidate genes have been studied to explore this relationship and converging evidence indicates the most likely contenders are genes linked to inflammation, neuroplasticity and the glucocorticoid stress response system. Major mood disorders like major depressive disorder and bipolar disorder are common and multifaceted neuropsychiatric conditions, typified by a wide array of symptoms. There is an increasing amount of data indicating that mood episodes are linked to the triggering of the innate immune system. There are several paths through which cytokines can access the brain, influence central neuronal functioning and cause behavioral changes typified by the "sickness behavior". In the pharmacological treatment of mood disorders, cytokine variations have key implications with regards to response or otherwise to these interventions.
Central fatigue and central regulation of performance
Shaun Phillips in Fatigue in Sport and Exercise, 2015
This chapter discusses some of the potential causes of central fatigue during exercise, before addressing a related concept, the central regulation of exercise performance. Pro-inflammatory cytokines may induce feelings of fatigue, lethargy, and sluggishness characteristic of many illnesses, and increased cytokine production during exercise could encourage similar sensations. Cytokine production can also influence central neurotransmitter production and function. A summary of exercise regulation as explained by the peripheral catastrophe model and the anticipatory regulation model. The anticipatory regulation model states that an initial exercise intensity is set prior to exercise, based on knowledge of exercise duration, experience, and afferent physiological feedback. During exercise, continual afferent feedback and awareness of remaining exercise duration allows a continued adjustment of motor unit recruitment and exercise intensity, allowing the athlete to maintain a neuromuscular and/or metabolic reserve that can be accessed in the final stages of exercise.
Losses of cytokines and chemokines are common genetic features of human cancers: the somatic copy number alterations are correlated with patient prognoses and therapeutic resistance
Published in OncoImmunology, 2018
Henry Sung-Ching Wong, Wei-Chiao Chang
Intricate relationships among cytokines (including chemokines) shape the tumor microenvironment (TME) and reflect cell-cell interactions between malignant cells and other cells from the TME. Although our previous study indicated the transcriptional landscape of cytokines in 19 cancer types, the global pattern somatic copy number (SCN) alterations and the clinical relevance of cytokines have not been systematically investigated. Here, we reported a significant negative selection on cytokine genes. We also linked the SCN losses of cytokine genes to the abundance of immune infiltrates which affects cancer progression and patient prognoses. We also demonstrated and validated the correlations between SCN alterations of cytokine-containing loci and drug sensitivity. The results indicated the genomic loss of cytokines in malignant cells as a crucial theme for interrogating cancer progression, malignant cell-TME interactions, and therapeutics.
Analysis of Th Cell-related Cytokine Production in Behçet Disease Patients with Uveitis Before and After Infliximab Treatment
Published in Ocular Immunology and Inflammation, 2017
Masaru Takeuchi, Yoko Karasawa, Kohzou Harimoto, Atsushi Tanaka, Masaki Shibata, Tomohito Sato, Rachel R. Caspi, Masataka Ito
Purpose: To examine antigen-stimulated cytokine production by Behçet disease patients (BD) before and after infliximab infusion. Methods: PBMCs were obtained before and after infliximab infusion in BD patients with or without recurrent uveitis during at least 1 year of infliximab therapy, and from healthy subjects. PBMCs were cultured with IRBP, and Th-related cytokines in cultures were measured. Results: Levels of IL-4, IL-6, IL-10 IL-17A, IL-17F, IL-31, IFN-γ, and TNFα were higher in BD before infliximab infusion than in healthy subjects, and these levels were the highest in BD with recurrent uveitis. After infliximab infusion, these cytokine levels were reduced to a greater extent in BD without recurrent uveitis than in BD with recurrence. Conclusions: Th-related cytokines produced by IRBP-stimulated PBMCs were elevated in BD, and infliximab infusion suppressed these cytokines to a greater extent in BD without recurrent uveitis than in those with recurrence.
Heparin and EDTA anticoagulants differentially affect the plasma cytokine levels in humans
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2013
Rahul Patil, Subodh Shukre, Ramesh Paranjape, Madhuri Thakar
Cytokines and chemokines are the cell signaling proteins which are considered as important biomarkers of inflammation and immunity. However the fragile nature of these markers results in the concentration variation due to various external factors. We assessed the influence of commonly used anticoagulants (EDTA and heparin) on various cytokine levels from 32 paired plasma samples using highly sensitive multiple cytokine estimation assay. Out of 17 cytokines estimated, 15 were detectable in more than 80% of the samples from both the groups. TNF-α, IFN-γ, IL-4, IL-5, and G-CSF levels were significantly higher (p values < 0.05 for all) in plasma with EDTA, whereas the levels of IL-6, IL-8, IL-10, IL-17, MIP-1β, GM-CSF and MCP-1 were found to be significantly higher (p values < 0.05 for all) in plasma with heparin. There was no significant difference in the levels of IL-7, IL-12 (P70) and IL-13 in both the groups. The study showed that the anticoagulants significantly affect the measurement of certain cytokines. Hence, it is important to choose an appropriate anticoagulant before the estimation of cytokines for reliable use of plasma cytokines as biomarkers in patient management.