Inflammation: The Good, the Bad, & the Ugly

by Bianca Garilli, ND, IFMCP

Too much inflammation can be a bad thing

When the topic of chronic disease comes up, the term inflammation is sure to be close behind. In fact, inflammation has received a fairly bad rap in the past years as research has underscored its prominent role in the promotion and perpetuation of many aspects of physiological dysfunction. Although not the root cause per se, inflammation has been shown to “add fuel to the fire” of a host of disease processes, playing a role in nearly all chronic illnesses.^1-4 Here are a few examples where inflammation “feeds the flames” of prevalent diseases:^1-4

• Certain types of cancers
• Cardiometabolic disease
• Asthma
• Autoimmune disorders
• Certain types of arthritis and pain
• Cognitive and mental health dysfunction

Timely and balanced inflammation can be a good thing

Interestingly, inflammation is not always a “bad thing” and, when expressed in a timely and correct manner, is an integral part of human health. In fact, appropriate, acute inflammation serves as a first line response to potential pathogens, it limits excessive tissue damage after trauma, and stimulates the body’s inherent repair processes.⁵

Dolor (pain), calor (heat), rubor (redness), and tumor (swelling) were initially identified in the first century AD by the Roman scholar Celsus as the four classic signs of the inflammatory process.⁶ A fifth cardinal sign, functio laesa (loss of function), was eventually added and thought to be attributed to Galen, although controversy remains over the original contributor.⁷

The body is naturally primed to respond to damage or infection through the acute inflammatory reactions of locally occurring cells that produce cytokines and other acute inflammatory mediators. These strategically placed immune cells respond to looming “danger” (infectious agents and trauma) by sending out a series of chemical messages to communicate the problem to various cell types located elsewhere throughout the body. At the same time, other cells are stimulated to release specific substances such as histamine, bradykinin, serotonin, and prostaglandins—each playing a unique role in inflammatory processes, such as the extremely important vasodilation of local blood vessels.⁸ When “reinforcements” (mainly neutrophils, sometimes eosinophils and others) from various locations answer the chemical signal and arrive to the scene, they are able to migrate directly through the vasodilated capillary walls (diapedesis), making it easier and more expedient for an acute response to occur.⁹

Healthy, acute inflammation stimulates healing

The benefits of this complex, orchestrated sequence of events is protection and repair to the damaged or infected tissues and can be characterized by the processes of “hemostasis and chemotaxis.”¹⁰ These processes reduce the risk of excessive bleeding, further damage, or spread of infection beyond the localized site.¹⁰ The acute inflammation stage typically lasts a matter of hours to days.¹⁰

In a synchronized dance and while initial steps of acute inflammation are still occurring, additional chemical signals are also being sent out to initiate critical phases of the healing process. The healing process can be characterized by two major phases—the proliferative phase and the maturation-remodeling phase:¹⁰

• The proliferative phase, which can last several weeks, is when granulation tissue is formed, and re-epithelialization and neovascularization occur within the damaged tissues.
• The maturation-remodeling phase is when strengthening of the scar tissue occurs for maximum impact.

Bacterial infection, an open tissue wound, and blunt trauma are just a few examples where these acute inflammation processes are both critical and beneficial. Acute inflammation plays a major role in human health, essentially discouraging further damage and supporting the healing process. Without an appropriate inflammatory response to infectious agents or trauma, healing is difficult and incomplete.

Resolving prolonged inflammation is critical

Unfortunately, when the inflammatory process goes awry or simply continues too long, this leads to the well-known term, “chronic inflammation,” along with its subsequent downstream chronic illness influences. In some cases, the cells associated with an appropriate inflammatory response fail to return, or resolve, to their pre-inflammation states; in other cases the inflammatory process is heightened and prolonged.¹¹ In both situations there is typically an external stimuli perpetuating the inflammation; this could be a persistent infectious agent, or in other cases, it may involve dietary interactions or toxic exposures. In many cases, the chemical milieu associated with obesity perpetuates the inflammatory molecules, leading to further downstream damage.^11-13

Maintaining a healthy and effective inflammatory response

There are two approaches to maintaining a healthy and effective inflammatory response: First, an appropriately timed and placed acute inflammatory process is required in response to infection and trauma and for initiating the healing process. Second, it’s critical that once the benefit of the acute inflammatory response has passed, that the molecular basis of the response returns to its pre-inflammatory state, rather than smoldering into a low-grade chronic inflammation state. This inflammation resolution is an active process facilitated by lipid mediators—specialized pro-resolving mediators (SPMs); this physiological process and the key players were discovered only a couple decades ago by Charles Serhan, PhD, DSc and colleagues.^14-16

Here are some specific steps related to lifestyle and personalized nutrition that can be implemented to support a healthy and effective inflammatory response and combat the chronicity of inflammation:^16-20

• Follow an anti-inflammatory dietary approach—variety of whole, minimally processed foods rich in fiber, brightly colored fruits and vegetables high in antioxidants and phytonutrients, and adequate intake of high-quality proteins and healthy fats, especially long-chain omega-3 fatty acids; some food plans avoid or limit gluten, soy, nightshades, dairy products, and sugars.
• Maintain a healthy weight and support lean and bone mass by participating in routine exercise and
• Limit exposure to endocrine-disrupting chemicals (EDCs) like obesogens whenever possible
• Make adequate and high-quality sleep a priority
• Avoid or limit chronic sources of stress and support healthy stress responses to avoid inflammatory stress molecule production
• Promote healthy gut barrier function through intake of prebiotics and probiotics
• Reduce oxidative damage to cells through sufficient or increased intake of antioxidants such as vitamins C, E, and A (beta-carotene) and phytonutrients
• Consider a personalized supplementation plan with anti-inflammatory actions in the body, such as omega-3s EPA and DHA, curcumin, xanthohumol, Boswellia serrata, ginger, and tetrahydro-iso-alpha acids (THIAA), and CoQ₁₀
• Consider a personalized supplementation plan that includes targeted nutraceuticals that support the resolution of inflammation, like SPMs, to target unresolved inflammation and turn off the damaging effects of long-term, low-grade chronic inflammatory pathways

Citations

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4. Felger JC et al. Imaging the role of inflammation in mood and anxiety-related disorders. Curr Neuropharmacol. 2018;16(5):533–558.
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8. Medline. Immune response. https://medlineplus.gov/ency/article/000821.htm. Accessed March 29, 2019.
9. Muller WA. Getting leukocytes to the site of inflammation. Vet Pathol. 2013;50(1):7–22.
10. Wallace HA et al. Wound Healing Phases. Treasure Island, FL. StatPearls Publishing. 2019. https://www.ncbi.nlm.nih.gov/books/NBK470443/. Accessed March 29, 2019.
11. Minihane AM et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr. 2015;114(7):999–1012.
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13. Pahwa R et al. Chronic Inflammation. Treasure Island, FL. StatPearls Publishing. 2019. https://www.ncbi.nlm.nih.gov/books/NBK493173/. Accessed April 3, 2019.
14. Serhan CN et al. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids vi cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med. 2000;192(8):1197-1204.
15. Serhan CN et al. Lipid mediators in the resolution of inflammation. Cold Spring Harb Perspect Biol. 2015;7(2):a016311.
16. Serhan CN. Pro-resolving lipid mediators in inflammation are leads for resolution physiology. Nature. 2014;510(7503):92–101.
17. Beavers KM et al. Effect of exercise training on chronic inflammation. Clin Chim Acta. 2010;411(11-12):785–793.
18. Nappi F et al. Endocrine aspects of environmental “obesogen” pollutants. Int J Environ Res Public Health. 2016;13(8):E765.
19. Calder PC et al. Inflammatory disease processes and interactions with nutrition. Br J Nutr. 2009;101 Suppl 1:S1-45.
20. Liu YZ et al. Inflammation: the common pathway of stress-related diseases. Front Hum Neurosci. 2017;11:316.

Bianca Garilli, ND, IFMCP is a former US Marine turned Naturopathic Doctor (ND). She works in private practice in Northern California and consults with naturopathic and Functional Medicine leaders, including the Institute for Functional Medicine and Metagenics. She is passionate about optimizing health and wellness in individuals, families, companies and communities- one lifestyle change at a time. Dr. Garilli has been on staff at the University of California Irvine, Susan Samueli Center for Integrative Medicine and is faculty at Hawthorn University. She is the creator of the Military and Veteran Health Initiative and is the current Past-President of the Children’s Heart Foundation, CA Chapter.