Tumor necrosis factor alpha or TNF-alpha (also sometimes written as TNF, TNFα, or cachectin) is part of a superfamily of related proteins called cytokines that cause systemic inflammation and are produced by many cells in the immune system.
Its name is derived from its original discovery that it caused tumor necrosis (i.e., tumor cell death) in certain animal model systems. Since then, multiple effects for this immune protein have been identified. Some of those effects include causing fever and muscle wasting, apoptosis (death of normal cells), autoimmunity (the misdirected immune response against the body), and organogenesis (the normal production and development of the body organs).
TNF-alpha has been shown to be often elevated in the serum of patients with ME/CFS compared to non-ME/CFS controls and is theorized to play a role with other cytokines in symptom presentation and severity.
Several clinical trials have been proposed for the use of a tumor necrosis factor-alpha inhibition drug, etanercept, in ME/CFS. Results have been mixed. A 2012 clinical trial at Haukeland University Hospital, Norway was terminated shortly after enrolling patients because two of the four patients experienced moderate worsening of symptoms after using etanercept as weekly subcutaneous injections. A pilot study in 2001 by K. Lamprecht using etanercept on six CFS patients reported considerable benefit, but the study was not expanded.
- 2016, Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women
"ABSTRACT: Objective - Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms. Methods - Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index. Results - Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β = 0.258, p = 0.043), IL-6 (β = 0.281, p = 0.033), and tumor necrosis factor-alpha (TNF-α) (β = 0.263, p = 0.044). Worse sleep quality related to greater fatigue severity (β = 0.395, p = 0.003) and fatigue-related interference with daily activities (β = 0.464, p < 0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β = 0.499, p < 0.001, and β = 0.556, p < 0.001, respectively). Conclusions - Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes."
- 1999, TNF-alpha and chronic fatigue syndrome
"ABSTRACT: Based upon the clinical presentation of chronic fatigue syndrome (CFS), we hypothesized that proinflammatory cytokines may play a role in the pathogenesis of the disease. We therefore undertook a retrospective cross-sectional study to examine the role of TNF-alpha in patients with CFS. Our results suggest a significant increase serum TNF-alpha in patients with CFS (P<0.0001) compared to non-CFS controls. This study supports the further examination of the role of proinflammatory mediators in CFS. Furthermore, the clinical testing of TNF-alpha blockers and other antiinflammatory agents for the treatment of this disease is warranted."
- 1994, Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression
"ABSTRACT: Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2 receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested. Nevertheless, only the distributions for circulating levels of TNF-alpha and TNF-beta differed significantly in the two populations. In patients with CFS--but not in controls--serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analyzed) with relative amounts (as compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6 (in order of appearance). These findings point to polycellular activation and may be relevant to the etiology and nosology of CFS."
- Locksley, Richard M.; Killeen, Nigel; Lenardo, Michael J. (2001), "The TNF and TNF Receptor Superfamilies", Cell, 104 (4): 487 - 501, doi:10.1016/S0092-8674(01)00237-9
- Wajant, H; Pfizenmaier, K; Scheurich, P (2003), "Tumor necrosis factor signaling", Cell Death and Differentiation, 2003 (10): 45–65, doi:10.1038/sj.cdd.4401189
- Moss, Ron B.; Mercandetti, Aristo; Vojdani, Alexander (1999), "TNF-alpha and chronic fatigue syndrome", Journal of Clinical Immunology, 19 (5): 314-6, PMID 10535608
- Patarca, Roberto; Klimas, Nancy; Lugtendorf, S; Antoni, Michael H.; Fletcher, Mary Ann (1994), "Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression", Clinical Infectious Diseases, 18: S147-53, PMID 8148443
- Lamprecht, K. "Pilot study of etanercept treatment in patients with chronic fatigue syndrome." Meeting of the American Associations of Chronic Fagitue Syndrome (AACFS). 2001.
- Milrad, Sara F.; Hall, Daniel L.; Jutagir, Devika R.; Lattie, Emily G.; Ironson, Gail H.; Wohlgemuth, William; Vera Nunez, Maria; Garcia, Lina; Czaja, Sara J.; Perdomo, Dolores M.; Fletcher, Mary Ann; Klimas, Nancy; Antoni, Michael H. (2016), "Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women", Journal of Neuroimmunology, 0 (0), doi:10.1016/j.jneuroim.2016.12.008