Inflammation is a defence mechanism initiated by the body’s immune system in response to perceived harmful stimuli such as trauma, infection and/or auto-immune disease.1 The purpose of inflammation is to initiate healing, making it crucial to both recovery and repair.
While acute inflammation is protective, low-grade systemic inflammation that is chronic, has been identified as a causal factor of many chronic diseases; in fact, more than half of all deaths are attributable to inflammation related diseases, these include cardiovascular disease, type 2 diabetes mellitus, autoimmune and neurodegenerative conditions.2
Acute versus chronic inflammation
Inflammatory challenges are encountered daily, however timely resolution of the acute inflammatory process is often under appreciated due to the innate ability of the body to repair. Inflammation that is acute typically starts rapidly and in response to injury. Inflammatory pathways are activated by the immune system leading to the release of cytokines as well as eicosanoids such as prostaglandins and leukotrienes derived from arachidonic acid. The recruitment of large numbers of leucocytes with neutrophils mediate inflammation and promote tissue repair. (See Figure 1)
Acute inflammation that is uncontrolled and unresolved becomes chronic, often lasting for prolonged periods of several months to years.
In chronic conditions, inflammation and repair occur concurrently, rather than consecutively, due to constant exposure to the irritant. Fibrosis and granuloma formation occur in combination with the destruction of tissue architecture. The dominant, infiltrating cell being the macrophage which functions to remove apoptotic neutrophils3 and restore homeostasis.
Resolution of inflammation versus reducing inflammation
When working with chronic inflammation in clinical practice, the focus has typically been on reducing inflammation, however, re-examining chronic inflammatory diseases through the lens of failed or dysregulated resolution is crucial to assist with resolution of inflammation.17
SPMs are molecules that are derived endogenously from arachidonic acid, docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are produced to counterbalance inflammatory cues.18 Unlike conventional anti- inflammatories, SPMs not only work by blocking the inflammatory process, but also by reprogramming immune cells and enhancing leukocyte efferocytosis, thus assisting with terminating and resolving the inflammatory process.19 (See Figure 2).
The turning point in the transition from an inflammatory to a non-inflammatory state is a switch in the synthesis of lipid mediators from pro-inflammatory lipid mediators to the synthesis of specialised pro-resolving mediators (SPM’s) during the acute inflammatory phase.18
When reducing inflammation does not work
While the switch from an inflammatory to a non-inflammatory state has been shown to occur in healthy individuals, it may not occur in individuals with a chronic inflammatory condition or dysbiosis.20 The pathways involved with the synthesis of SPMs from omega-3 fatty acids are impaired. In these individuals, a focus on reducing inflammation rather than resolving inflammation may be ineffective.
Barden et al. (2019)21 observed that individuals with metabolic syndrome and obesity demonstrated dysregulated inflammatory pathways, preventing them from making adequate SPMs required to resolve inflammation. This was remedied with weight loss and improving insulin sensitivity.
Holistic treatment of inflammation
Green space
Immersion in nature is associated with a more favourable inflammatory profile. Serum levels of interleukin-8 (IL-8) and TNF-α were significantly decreased after 2 hours of exposure to a forest environment in stressed young adults compared to placebo.22 This is hypothesised to be due in part to exposure to anti-inflammatory terpenes released from trees which block the inflammatory cascade.23
Sauna
An inverse, dose–response relationship has been found between regular use of sauna and reduced levels of CRP.24 Acute exposure to heat increases IL-6, triggering the release of interleukin-10 (IL-10), inhibiting several pro-inflammatory cytokines.25
Connection
Relationships that are characterised by connection and support are associated with lower levels of systemic inflammation compared to individuals who experience unsupportive or hostile relationships.26 Higher levels of IL-6 & TNF-a were observed in couples experiencing sustained marital conflict.27
Movement & stretching
Both exercise and stretching have been shown to assist with the resolution of acute inflammation by enhancing the production of SPMs and promoting macrophage phagocytosis in vivo.28,29
Diet
Dietary patterns that emphasise a whole food diet such as the Mediterranean diet are associated with lower levels of inflammatory cytokines, CRP and TNF-α.30 Key components include; seasonal fruits and vegetables, herbs & spices, anti-inflammatory fats such as extra virgin olive oil31 as well as omega-3 rich fish.
Supplementation
Targeting both reducing inflammation and resolving inflammation would appear most efficacious when managing chronic inflammatory conditions. In an open-label pilot study, involving 29 individuals with inflammation-associated discomfort, consumption of a combined SPM-enriched marine oil and curcumin supplement taken daily for 60 days resulted in a significant reduction in pain.32
Working with patients to identify triggers for both acute and chronic inflammation, and addressing the root cause of inflammation is key to reducing inflammation. For those patients already in a state of chronic inflammation, enhancing SPM levels both endogenously and exogenously supports the reduction in ongoing inflammation and is supported by dietary and lifestyle changes, where needed. Supporting patients through the supplementation of SPMs can accelerate this process and should be considered a first-line treatment for chronic inflammation.
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