Cytokine Dysregulation, Inflammation and Well-Being

Abstract

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic ‘overshooting’ with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-α and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the ‘systemic anti-inflammatory feedback’ and/or ‘hyperactivity’ of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.

Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation: A Twin Study

“…Our work substantiates the suspicion that there may be shared etiological mechanisms across chronic conditions, and that a key link may be a shared genetic vulnerability to inflammation (24;25). This might be true for other chronic conditions, such as CHD, diabetes, cancer and neurodegenerative diseases (50). Our results also provide a clue for the inconsistencies in previous literature concerning the association between MDD and inflammation (21), since results may vary depending on genetic admixture and population stratification.…”

Biomarker responses to weaning stress in beef calves

“…CXCL8 is an important inflammatory mediator, predominantly responsible for the chemotaxis of neutrophils, although it also functions in T cell migration (Elenkov et al, 2005;Keller et al, 2005). In the present study, CXCL8 increased in control and weaned calves, indicating a non-specific response to stress.…”

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

“…Whereas appropriately regulated inflammation-tailored to stimulus and time [4]-is beneficial, excessive or persistent systemic inflammation incites tissue destruction and disease progression [5].…”