The Physiological Role of Tumor Necrosis Factor in Human Immunity and Its Potential Implications in Spinal Manipulative Therapy: A Narrative Literature Review

Abstract

Objective: Although tumor necrosis factor (TNF) is a well-known inflammatory cytokine in the pathological development of various human diseases, its physiological roles are not widely understood nor appreciated. The molecular mechanisms underlying spinal manipulation therapy (SMT) remain elusive. The relationship between TNF and SMT is unclear. Thus, we performed this literature review to better understand TNF physiology and its potential relationship with SMT, and we propose a novel mechanism by which SMT may achieve clinical benefits by using certain beneficial features of TNF. Methods: We searched several databases for relevant articles published between 1975 and 2015 and then reexamined the studies from current immunophysiological perspectives. Results: The history and recent progresses in TNF physiology research were explored. Conflicting reports on the relationship between TNF and SMT were identified. Based on the newly discovered interaction between TNF and regulatory T cells, we proposed a putative biphasic TNF response to SMT, which may resolve the conflicts in the reported observations and interpretations. Conclusion: The current literature about TNF informed our discussion of new physiological roles for TNF, which may help to better understand the physiological effects of SMT. (J Chiropr Med 2016;15:190-196)

Re-Examining the Role of TNF in MS Pathogenesis and Therapy

“…TNF is a pleiotropic cytokine increasingly recognized to regulate important physiological processes not only in the immune system, but also in the brain [ 9 , 10 , 11 ]. Evidence for TNF involvement in MS includes the identification of TNF in astrocytes, microglia, and endothelial cells, preferentially in acute and chronic active MS brain lesions and in the cerebrospinal fluid (CSF) of MS subjects [ 12 , 13 , 14 ].…”

The Effects Induced by Spinal Manipulative Therapy on the Immune and Endocrine Systems

“…It has been reported that a possible explanation for of such contradictory data between these two studies [23,28] may be due to different methods in culture systems (i.e., incubation period) and doses of the inducer (i.e., endotoxin) [58].…”

“…It is likely that, in normal CNS sensitivity conditions, an increase of these signaling chemicals after SMT may lead to transient adverse effects (e.g., soreness, fatigue), whereas in circumstances of hyperexcitability, like in chronic pain states, such increase may drive to an escalation of events leading to pain exacerbation [58].…”

Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic Care on the Neuroendocrine-Immune System

“…As with the keyword search term “cytokine” above, other unique keyword searches that directly relate to “immunity” such as interleukin and interferon are considered separately in more individual detail in the following sections. Twenty-seven references were identified in our search describing the relationship between chiropractic care and various aspects of immune function: 12 case studies, five research trials, and 10 reviews [ 85 , 93 , 96 , 122 - 145 ]. Of these original research studies meeting our inclusion/exclusion criteria, notable findings include one early set of pilot studies that report trends towards shifts in blood markers/CBCs in adjusted subjects [ 124 , 125 ], and another trial that reports lymphocytic activation in adjusted subjects as compared to control [ 132 ].…”