Nutrition and Inflammation

Fig. 8.1

Relationships between nutrition, inflammation and immunity, and oral health
There is general agreement that a broader understanding of the nutrition, inflammation, and oral heath triangle is indicated due to potential implications for clinical practice and patient care. In this chapter, we present the current research and theories pertaining to the relationships between nutrition, inflammation, and oral health. In addition, we aim to highlight those areas that are supported by strong data while drawing attention to areas that merit further study.

Definitions of Terms

According to Navia [1], nutrition is “a complex science that involves not only food and diets, but also makes use of principles from biochemistry, genetics, immunology, physiology, and molecular biology to deal with the process of incorporating into the body essential compounds from the trophic environment that cannot be synthesized by the human tissues.” Malnutrition represents the “pathophysiological consequences of the ingestion of inadequate, excessive, or unbalanced amounts of nutrients or impaired use of ingested nutrients” [2]. It results in an imbalance between the supply of nutrients and energy and the physiologic demands of the body to ensure growth and function [3].
Inflammation is broadly defined as a host reaction elicited in response to tissue injury [4]. This reaction is characterized by a release of substances from neighboring cells that defend the host against further injury and facilitate tissue healing and repair [5]. Inflammation can assume two forms—acute and chronic—that differ by onset, duration, and cellular composition. Acute inflammation is generally rapid in onset, short in duration, and characterized microscopically by emigration of leukocytes (most notably neutrophils) accompanied by an exudate of fluid and plasma proteins [5]. In contrast, chronic inflammation is typified by slow onset and long duration. The inflammatory infiltrate is predominated by lymphocytes and plasma cells [5] though with prolonged inflammation, other cell types such as fibroblasts are recruited to the site of injury, which contribute to fibrosis and tissue necrosis [5, 6]. The classical hallmarks of inflammation include dolor (pain), calor (heat), rubor (redness), tumor (swelling), and functio laesa (loss of function). Though inflammation is primarily a protective function of the host, the same mechanisms involved in defense and tissue repair can produce harmful and pathologic changes in the body in a true dualistic manner [7]. Inflammation is closely intertwined with immunity, immune function, and infection. As such, these interrelated processes are discussed in tandem in this chapter.
The Immune System and the Immune Response
The immune system represents a specialized collection of proteins, cells, tissues, and organs that is responsible for defending the host against infection and executing the immune response. The immune response is broadly divided into the two major arms—innate and adaptive. Innate immunity represents the body’s immediate defense against infection and first-line barrier to microbial assault. The major components of the innate immune response include the epithelial cells, phagocytic leukocytes such as neutrophils and macrophages, the natural killer (NK) cell, and a variety of plasma proteins such as the complement system proteins [7]. Adaptive immunity is a more specific response that “adapts” to the presence of an infection. In addition to aiding in the elimination pathogens, it also allows for recognition and protection against future challenges by the microbe [7]. The adaptive immune response is further subdivided into two types—humoral immunity, which is mediated primarily by the antibodies produced by B lymphocytes, and cell-mediated immunity, which is mediated by T lymphocytes and their subsets [7]. The cellular reactions that result from innate and adaptive immunity culminate in inflammation [7].
The immune response is initiated and propagated by an integrated series of pro- and anti-inflammatory cascades that require participation of key inflammatory cells and chemical mediators. Biologically active chemical mediators play an integral role in directing and coordinating the inflammatory response. These signaling molecules are produced in response to inflammatory stimuli [8] and have diverse roles in growth, differentiation, host defenses, and tissue damage. The molecules bind to target cells via receptors and orchestrate a sequence of events, including but not limited to altering vascular permeability, increasing neutrophil chemotaxis, stimulating smooth muscle contraction, and mediating oxidative activity [5]. Their effects may be beneficial or detrimental depending on the clinical setting in which they are elicited [9]. Production of the mediators is tightly regulated by an array of control systems that require the participation of various organs, including the liver, brain, adrenal cortex, and immune system [9]. Precise control of mediator production and activity is crucial as disruptions and imbalances can lead to ineffective or exaggerated immune responses and may result in tissue damage and overall harm to the body. Examples of chemical mediators include the vasoactive amines such as histamine, arachidonic acids such as leukotrienes, and cytokines such as tumor necrosis factor (TNF) and interleukins [5]. We will herein focus on selected mediators of relevance to the nutrition, inflammation, and oral health relationship. A more comprehensive review of chemical mediators and their actions can be found in several excellent immunology texts [10, 11].
Infection, Inflammation, and Immune Function
Infection represents the invasion of a host by a pathogenic organism, resulting in cellular injury due to competitive metabolism, production of toxins, intracellular replication, or the effects of antigen–antibody responses. Though the relationship between infection, inflammation, and immunity is complex, it may be helpful from an explanatory standpoint to view inflammation as the link between infection and the immune response. A clearer relationship exists between infection and immune function whereby impaired immunity intensifies infectious processes [8] and optimal immune function protects against infection. Nutritional imbalances can influence this relationship by affecting the availability of nutrients, which in turn impacts the production and activity of the inflammatory mediators that coordinate the immune response [8].

Relationship Between Nutrition, Inflammation, and Immune Function

The relationship between nutrition and inflammation has been examined extensively over the past five decades. The result is an impressive body of the literature that supports a strong and dynamic link between the two, characterized by common pathways of activation and regulation. Historically, research efforts have centered on the influence of undernutrition on inflammation and immune function and specifically, on the promotion of immune incompetence and infection in the setting of nutritional deficiencies [12]. However, the growing epidemic of obesity and obesity-related complications has prompted a shift in focus toward the effects of overnutrition on systemic health, inflammation, and immunity.

Impact of Nutrition on Inflammation and Immune Function

The role of nutrition in inflammation has been recognized for decades and continues to be an active area of nutrition- and immunology-based research. The reader is referred to the authoritative text “Nutrition and Immunology” [13] and to the “Diet and Human Immune Function” [14] and “Dietary Components and Immune Function” [15] editions of this Nutrition and Health series which provide excellent and comprehensive reviews on this topic.
The capacity for nutrients to modulate immune function bears significant clinical and public health implications [12, 16]. One of the earliest proposals that nutritional status was linked to the immune system was put forth by Scrimshaw et al. [3] in their 1968 World Health Organization monograph. This publication followed seminal work performed by the same investigators nearly a decade earlier that documented primarily synergistic, occasionally antagonistic, interactions among malnutrition, infection, and host immune responses [17]. As knowledge of immunology was relatively rudimentary prior to the 1970s, this group’s observations were considered truly groundbreaking and remain relevant today [18]. Better characterization of the interrelationships between nutrition, immunity, and infection has since been enabled by refinement of immunologic and molecular techniques [18]. It is increasingly apparent that nutrition can affect host immunity on many different levels, including initial development and subsequent function. As such, nutrition may be best viewed as exerting a constant influence on immune-regulated processes.

Undernutrition, Inflammation, and Immune Function

It is important to note that the relationship between malnutrition and immune function is not strictly unidirectional. Rather, there appears to be a cyclical interaction that exists among nutrition, immunity, and infection whereby undernutrition provokes immune dysfunction, compromised immunity predisposes to infectious diseases, and infection further promotes nutrient deficiencies [8]. The global effects of this vicious cycle are seen most lucidly—though not exclusively—in the lower socio-economic classes, where the spiral of malnutrition, infection, disease, and debilitation reduces productivity and exacerbates already impoverished conditions [19].
Adequate nutrition in childhood is essential for proper development and maturation of the immune system [20]. Keusch [21] observed early involution of the thymus gland in children suffering from undernutrition. Chandra [22] demonstrated both a numerical and functional deficiency of CD4+ T-helper cells and moderate decreases in CD8+ T cells [12] in protein energy deficient children, postulating that this was likely due to reduced thymic factor activity. In concordance with these findings, Savino [23] observed diminished thymic development and reductions in peripheral lymphocyte counts in children with severe nutritional deficiencies. Malnutrition-induced reductions in mature T lymphocytes have then been associated with long-term compromises in cell-mediated immunity and diminished T-cell-dependent antibody responses [21] leading to the so-called “nutritionally acquired immunodeficiency syndrome.”
In addition to influencing the initial development of the immune system, nutrition also plays a vital role in ensuring the proper function of subsequent immune and inflammatory responses. Nutritional imbalances may interfere with immune function through a variety of mechanisms, including alterations in antibody production; cell-mediated immunity; phagocyte, complement, and T-cell activity; and nonspecific host defenses [18]. Table 8.1 summarizes the effects of select macro- and micronutrients on immune function [18, 24]. Regrettably, a complete description of all nutrients and their roles in immune function is beyond the scope of this text. The reader is referred to excellent reviews by Enwonwu [25], Grimble [26], and Scrimshaw and SanGiovanni [18] for more detailed information. We will herein focus on the immunomodulatory effects of protein deficiency.

Table 8.1

Effects of macronutrients and micronutrients on immune function
Cell/function affected
Protein (deficiency)
All components of immune system
Depression of cell-mediated immunity
Dysfunction of B cells, macrophages, neutrophils, complement
Effects on cytokine production
Amino acids (deficiency)
Functional changes in humoral immunity
Depletion of cells of lymphoid tissues (sulfur-containing amino acids deficiencies)
Impaired wound healing (linoleic acid deficiency)
Stimulation of suppressor T cells (linoleic acid excess)
Improvement of cell-mediated immunity (omega-3 fatty acid excess)
Cell/function affected (animals and humans)
Vitamin A (deficiency)
Reduced NK activity
Lower production of interferon
Impairment of delayed cutaneous hypersensitivity
Reduction in lymphocyte count; atrophy of lymphoid tissues (thymus, spleen)
Reduced mobility of peripheral macrophages
Vitamin B6 (deficiency)
Depression of cell-mediated immunity functions
Depression of antibody production after immunization
Reduction in lymphocyte count; atrophy of lymphoid tissues
Diminishment of inflammatory response
Vitamin C (deficiency)
Impairment of neutrophil and macrophage function
Reduction in thymic humoral factors
Depression in T-lymphocyte response, complement function
Impairment of delayed cutaneous hypersensitivity
Compromised epithelial integrity
Vitamin E (deficiency)
Depression in humoral response, B cell function
Reduced lymphocyte and leukocyte killing power
Depression in T-lymphocyte response, phagocyte function
Impairment of delayed cutaneous hypersensitivity
Depression of cell-mediated immunity functions
Zinc (deficiency)
Marked atrophy of thymus
Reduction in leukocytes
Depression of cell-mediated immunity functions
Depression in T-lymphocyte response, phagocyte function
Impairment of delayed cutaneous hypersensitivity
Impairment of cytokine or lymphokine function or production
Selenium (deficiency)
Impairment of antibody production
Reduction in bactericidal activity of neutrophils
Impaired synthesis of antioxidants
Iron (deficiency)
Depression of humoral response, B cell function
Depression of T-lymphocyte response
Impairment of delayed cutaneous hypersensitivity
Magnesium (deficiency)
Depression of humoral response, B cell function
(primarily animal)
Depression of cell-mediated immunity functions
Depression of T-lymphocyte response, phagocytic function
Impairment of cytokine or lymphokine function or production
Adapted from Scrimshaw and SanGiovanni [18] and Raiten [24]
Protein Energy Malnutrition
Protein energy malnutrition (PEM) is defined as a state of nutrition in which a deficiency or imbalance of energy, protein, and other nutrients causes measurable adverse effects on the body, function, and clinical outcomes [3]. Traditionally, the term PEM was used to describe a spectrum of conditions that were broadly subcategorized into three clinical forms: kwashiorkor (protein-predominant deficiencies), marasmus (protein deficiency and caloric insufficiency), and marasmic kwashiorkor (marked protein and calorie deficiencies) [27]. The effects of PEM on the immune system are profound and involve changes in both innate and adaptive immunity [8]. In PEM, the defense mechanisms primarily targeted are cell-mediated immune function, phagocyte function, T-cell responsiveness, NK cell lytic activity, delayed hypersensitivity, complement system activation, antibody formation and secretion, and cytokine production [8, 12, 18, 22, 28, 29]. These findings have been supported in both experimental models of PEM and clinical studies of protein-deficient individuals [28]. Moreover, malnutrition has been shown to affect the closely intertwined endocrine system by eliciting increased production and secretion of stress hormones and decreased secretion of insulin [8]. Fluctuations in these hormones can further compromise immune competence. For example, elevated glucocorticoid levels can induce macrophage dysfunction and inhibit transcription, expression, and secretion of various cytokines and proteins critical in regulating inflammation [8, 30].
Historically, it was presumed that patients suffering from PEM were susceptible to immune dysfunction because of a lack of endogenous nutrient stores necessary for sustaining host resistance processes [28]. However, it has become increasingly evident that modulation of cytokine biology is largely responsible for nutrition-induced effects on immune function. Malnutrition and in particular, protein deficiency has been associated with altered levels of key inflammatory cytokines such as interleukins (IL), tissue necrosis factors (TNF), and interferons [8, 18, 31]. These cytokines perform their functions in a highly integrated manner and are capable of producing a wide range of metabolic and immune effects [26]. Proposed mechanisms through which PEM may alter cytokine levels include modulation of antioxidant defenses and attenuation of the acute-phase response [32].
PEM and Antioxidants
Antioxidants are substances that neutralize a variety of reactive intermediates such as oxidants and free radicals. Oxidants (also known as oxidizing agents and oxidizers) are agents with oxidizing capabilities that include a large class of molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). The role of oxidants in inflammation and immune stimulation overlaps significantly with free radicals and cytokines [9, 16]. Collectively, these highly potent molecules destroy pathogens and eradicate damaged and/or aberrant cells, thereby facilitating restoration of normal tissue function [16]. Furthermore, these substances share a complex, synergistic relationship through which each can stimulate and enhance the other’s production and activity [16]. A crucial mediator in this crosstalk appears to be nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [16], a family of inducible transcription factors that modulate expression of over 180 mammalian target genes [33]. NF-κB activation can occur in response to a variety of stimuli, including the actions of inflammatory cytokines, immune-related stress induced by conditions like bacterial infections, oxidative stress, and many others [33]. It is believed that activation of these factors represents an important pathway for cellular adaptation to these stresses [33]. Well-known inducers of NF-κB include TNF and its associated inflammatory kinases [33].
While the actions of oxidants, free radicals, and certain cytokines are primarily beneficial in the body’s defense mechanism, the relationship can rapidly shift to a deleterious one if there is overproduction of either or control systems become deregulated [9]. Antioxidants contribute to minimizing oxidative stress by inhibiting oxidation and maintaining oxidant and cytokine levels within healthy confines [9]. Insufficient levels of antioxidants can alter the antioxidant–oxidant balance in favor of oxidant excess and indirectly modify cytokine-mediated responses to inflammation and infection. This can lead to disturbances in the normal redox state of cells and cellular damage known as oxidative stress.
PEM diminishes the substrate stores necessary for the production of antioxidants [16]. Amino acids with sulfur moieties like methionine and cysteine are of particular importance because they form the building blocks of a key antioxidant known as glutathione [16]. Deficiencies in the sulfur-containing amino acids and other essential nutrients such as selenium [16], zinc, and vitamins E, A, and D, can impair glutathione synthesis. Glutathione is an essential, endogenous antioxidant that participates in a wide array of metabolic and biochemical reactions [34]. In addition to neutralizing free radicals through glutathione peroxidase and catalase [16], glutathione influences the immune response on several levels, including cytokine production, leukotriene synthesis, lymphocyte proliferation, cytotoxic T cell and NK cell function, and maintenance of other antioxidants in their active form. The importance of glutathione in homeostatic control of various systems becomes apparent when examining patients who suffer from deficiencies in glutathione synthetase and the glutathione S-transferases (GST), the enzymes involved in the synthesis and conjugation of glutathione, respectively. Patients affected with glutathione synthetase deficiency (GSD) exhibit hematologic, metabolic, neurologic, and immune abnormalities [35]. Decreased cellular levels of glutathione have also been documented in diabetes mellitus, cancer, and HIV infection [36]. Deficiencies in GST can also be associated with a variety of clinical complications. The GSTs are a family of enzymes that catalyze conjugation of reduced glutathione, thereby aiding in the detoxification of reactive electrophiles, products of oxidative stress, and carcinogens [37, 38]. The pathologic manifestations attributed to deficiencies in both enzymes are presumably related to increased oxidative stress compounded by a diminished capability to cope with oxidative stress, resulting in accumulation of ROS and noxious substances in target cells [37].
PEM and Acute-Phase Proteins
The acute-phase response (APR) is an essential component of a host’s immune reaction to tissue injury [25]. In addition to generating nonspecific responses like fever and elevations in peripheral leukocyte counts [25], the APR is also characterized by increased secretion of various hormones such as corticotropin-releasing factor and hepatic synthesis of vital proteins known as acute-phase proteins [25, 26, 39, 40]. The magnitude of the APR varies depending on the severity of inflammation and extent of tissue injury [25].
Activation of the APR is characterized by increased hepatic synthesis of the acute-phase proteins (APPs) [8, 25],which include c-reactive protein (CRP), serum amyloid A (SAA), α1-acid glycoprotein, α2-macroglobulin, ceruloplasmin, metallothionein, and the complement proteins, among others [25, 26]. Collectively, the APPs modulate the immune response by enhancing antioxidant defenses, activating complement pathways [41], and interacting with and modifying the properties of various cytokines [42].
Production of APPs requires adequate dietary intake of proteins and amino acids, trace elements and vitamins, and energy [8]. As with antioxidants, APP synthesis is highly dependent on the availability of essential amino acids like glycine, serine, and the sulfur-containing amino acids methionine and cysteine [8]. These amino acids are typically limited in the setting of PEM [8]. APP production may be further impaired by PEM-induced reductions of certain cytokines such as IL-1 and IL-6 as cytokine levels are believed to be the primary stimulus for APP synthesis [25]. Overall reduction in APPs in conjunction with diminished cytokine levels culminate in APR attenuation. This has been observed in children suffering from even mild malnutrition who are challenged with infection [43]. Ultimately, severe blunting of APR may be associated with grave consequences given its crucial role in tissue healing after injury [25, 43].

Overnutrition, Inflammation, and Immune Function

There is also convincing evidence to show that excessive ingestion of nutrients and energy can have negative implications on inflammation and the immune response. Excess fat—both dietary and stored—can give rise to a plethora of complications. This emphasizes the importance of maintaining an optimal balance between nutrition, inflammation, and immune function [44].
Exogenous Fat: Dietary Fat and Fatty Acids
Dietary fat and fatty acids can exert potent effects on metabolism and inflammation through influence on cytokine production, production of other lipid-derived mediators, and alteration of tissue responses to these mediators [9, 32]. The immunomodulatory effects of fatty acids have been discussed elsewhere in several excellent references [15, 45]. To summarize, there are four types of fatty acids of significance in immune function—(1) Saturated fatty acids such as steric and palmitic acid, (2) ω-9 monounsaturated fatty acids such as oleic acid, (3) omega-3 polyunsaturated fatty acids (ω-3 PUFAs) such as α-linolenic acid and eicosapentaenoic (EPA), and (4) omega-6 polyunsaturated fatty acids (ω-6 PUFAs) such as linoleic acid and γ-linolenic acid [9].
Studies have shown that diets rich in ω-3 PUFAs and poor in ω-6 PUFAs reduce proinflammatory cytokine production and responsiveness [9], resulting in an overall immunosuppressive or anti-inflammatory effect; likewise, diets rich in ω-6 PUFAs are associated with increased proinflammatory cytokine production and responsiveness [9] and generate an overall proinflammatory state. It has been postulated that these changes in cytokine biology are related to shifts in fatty acid composition of membrane phospholipids, a process that is primarily regulated by dietary fat intake [32]. Compounds then formed from the hydrolysis of the membrane phospholipids harbor the innate ability to modulate cytokine production and activity [46]. The anti-inflammatory actions of the ω-3 PUFAs have been ascribed to a decrease in the production of inflammatory cytokines as well as classic inflammatory mediators such as arachidonic acid-derived eicosanoids (prostaglandin E2) and [47, 48]. ω-3 PUFAs also serve as key substrates capable of being converted to a group of lipid mediators with potent anti-inflammatory properties known as the resolvins and protectins [4952]. The actions of these mediators, particularly resolvins, appear to be diverse but at least partially involve a reduction of upstream proinflammatory cytokines [51]. In recognizing the anti-inflammatory potential of these lipid mediators, researchers have begun to explore the ω-3 PUFA supplementation as a therapeutic option in various inflammatory diseases. The beneficial effects of administering the ω-3 PUFAs in conjunction with aspirin, which enhances the activity of the lipid mediators through its actions on cyclooxygenase-2 (COX-2), has been demonstrated in vitro and in vivo via inflammatory-disease-animal models [5356]. Meydani et al. [57] found that fish oil capsules containing ω-3 fatty acids given to both younger and older females diminished the ability leukocytes to produce IL-1, IL-6, and TNF-α. Supplementation with ω-3 PUFAs in the form of fish oil have also been shown to mitigate inflammatory symptoms in rheumatoid arthritis, psoriasis, asthma, atherosclerosis, Crohn’s disease (CD), and ulcerative colitis [26, 51].
Endogenous Fat: Excess Body Fat and Obesity
Excessive intake of dietary fat and calories also contributes to accumulation of excess stored fat within the body. The multifaceted role of adipocytes in homeostatic processes and metabolism has become a subject of extensive study over the past two decades. The complex actions of these cells are primarily coordinated by the synthesis and release adipose-derived peptide hormones (so-called “adipokines”), making adipose tissue akin to an endocrine organ rather than a simple energy storage depot as previously believed [58]. These fat-derived substances function in both metabolism and immunity [44] by influencing the immune response, energy balance and glucose regulation, and other cellular processes. Individuals who suffer from adipocyte imbalances are therefore predisposed to the wide array of conditions. These include obesity-related inflammatory disorders, atherosclerosis, and diabetes mellitus [59].
Endogenous fat may influence inflammation and immune function through two main pathways—generation of endoplasmic reticulum (ER) stress and production of ROS. ER stress is a fundamental route through which intracellular inflammatory pathways can be engaged [44]. Increased adiposity imparts higher demands on the ER that leads to generation of ER stress [6062]. ER stress has been shown to activate key inflammatory kinases such as c-Jun N-terminal kinase (JNK) and inhibitor of NF-κβ (IKK) [44, 63]. These kinases perform the critical function of integrating signals from multiple inflammatory mediators [44, 63] and acting as cross-communicators between the metabolic and immune arms [44]. The ER is therefore considered a crucial site for detecting metabolic stress and translation to an inflammatory response [62]. In addition, the ER is a major source of ROS [62, 64].
The second and related pathway through which excess fat modulates inflammation is generation of ROS. It has been shown that increased adiposity and prolonged hyperglycemia trigger production of ROS [63, 65], including the redox-sensitive gene transcription factors nuclear factor-κβ (NF-κβ) and activating protein-1 (AP-1) [65]. High levels of ROS lead to increased oxidative stress [66] which is associated with proinflammatory sequelae [65]. Moreover, long-term derangements in oxidative stress have been shown to contribute to insulin resistance and chronic hyperglycemia, leading to formation of advanced glycation end products (AGEs) and further generation of ROS and oxidative stress in a feed-forward mechanism [67]. Thus, the mechanistically linked pathways of ER stress and ROS operate in a concerted manner toward a common endpoint—a state of hyperinflammation. This supports the increasingly accepted concept that metabolic signals are the likely triggers of inflammatory responses in the setting of metabolic excess [62].
There are significant commonalities between adipocytes and immune cells, from phagocytic potential to complement activation. Both fat and immune cells are capable of secreting mediators such as TNF-α, IL-6, and others, which are involved in both immunity and metabolism [44, 62, 63]. Adipocytes can also produce chemotactic signals that lead to recruitment of inflammatory cells [63]. Hence, adipose tissue can be viewed as a site of inflammatory cell recruitment and accumulation, production of cytokines (so-called “adipokines”), and interaction of fat cells with other effectors of inflammation [62]. Additionally, it appears that the inflammatory response that occurs in the presence of excess adipose tissue is triggered by and resides in the adipocytes themselves [62]. This highly integrated relationship between adipocytes and immune cells is the likely mechanism through which excess adipose tissue is linked to its inflammatory sequelae [63].
Obesity is broadly defined by the World Health Organization (WHO) as abnormal or excessive fat accumulation that may compromise health [68]. Early rodent models provided the first molecular evidence of a link between obesity, obesity-related insulin resistance, and inflammation [44]. Investigations utilizing these models revealed overexpression of TNF-α in adipose tissue [69, 70], a finding that was later verified in humans [71]. In addition, study of loss and gain of function models demonstrated that upregulated TNF-α impaired insulin action while absence of TNF-α improved insulin sensitivity, respectively [69, 72]. Subsequent studies have confirmed similar roles for other inflammatory mediators that are overexpressed in the setting of excessive adipose tissue, including IL-6, leptin, monocyte chemotactic protein (MCP)-1, and others [44]. Table 8.2 [44] summarizes the immunomodulatory effects of factors expressed or reduced in obesity. The reader is referred to a review of obesity-related factors involved in metabolism and immunity by Wellen and Hotamisligil [44] for more detail on this topic. Beyond individual cytokines and mediators, obesity has also been associated with activation of key inflammatory kinases like JNK and IKK [44]. These kinases can be further stimulated by lipid-induced elevations in proinflammatory cytokines, effecting a self-perpetuating cycle of increased adiposity and inflammation [63]. These investigational findings were pivotal in establishing a relationship among inflammation, metabolism, and obesity and suggest that inflammation may be the common denominator that links obesity to its pathologic and immunologically related consequences [63]. In recognizing this relationship, researchers have now begun to explore the possibility of manipulating adipocyte biology to selectively activate or inhibit immunologic factors such as the cytokines, inflammatory kinases, and more central processes like ROS and ER stress. This may represent a powerful approach to managing and perhaps even preventing obesity-related inflammatory conditions.

Table 8.2

Immunomodulatory factors in obesity
Metabolic regulation
Increased in obesity
Promotes insulin resistance
Increased in obesity
Multiple effects on inflammation
Promotes insulin resistance
Increased in obesity
Multiple effects on immune function
Promotes fatty acid oxidation
Adiponectin sensitivity
Decreased in obesity
Anti-inflammatory; promotes insulin sensitivity
Increased in obesity
Early B cell growth factor
Increased by hyperglycemia
Proinflammatory; regulates insulin secretion
Increased in obesity
C-reactive protein
Increased in obesity
Proinflammatory; atherogenic
Adapted from Wellen and Hotamisligil [44]

Impact of Inflammation and Immune Function on Nutrition

Inflammatory processes can impact nutrient intake and utilization starting with local effects in the oral cavity. The impact of localized inflammatory processes on nutrition is best seen in immune-mediated oral disorders like recurrent aphthous stomatitis and the vesiculo-erosive conditions lichen planus, pemphigus vulgaris, mucous membrane pemphigoid (MMP), and systemic lupus erythematosus. Individuals affected by these conditions may limit their dietary intake and consequently develop nutrient deficiencies secondary to their inability to eat an adequate diet (also covered in Chapters 5, 12 and 15). An additional group of inflammatory diseases that have significant impacts on nutrition are the inflammatory bowel diseases (IBD). The IBDs represent a family of clinically diverse conditions that are characterized by chronic, primarily cell-mediated inflammation that leads to damage of the gastrointestinal (GI) tract [73]. The two principal forms of IBD are ulcerative colitis and Crohns Disease (CD). We will herein focus on CD.
The pathogenesis of the underlying inflammatory changes seen in CD is complex and involves a synchronized interplay of bacterial provocation, genetic susceptibility, immune dysregulation, and environmental triggers [73]. Pivotal events that lead to the initiation of inflammatory changes include upregulation of various inflammatory pathways and persistent activation of mitogen-activation protein kinase (MAPK) and NF-κB signaling [73]. The subsequent release of proinflammatory cytokines such as TNF-α, interferon (IFN)-γ and chemokines, lead to activation of T cells and other immune cells. This is followed by secretion of enzymes that degrade the extracellular matrix and facilitate an influx of inflammatory cells and proinflammatory mediators [73]. These events correlate closely with the pathognomonic transmural (full-thickness) inflammation seen on microscopic examination of CD-affected intestinal mucosa.
Malnutrition affects 20–75% of individuals with IBD and is particularly prevalent in patients with CD [73

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Nov 4, 2015 | Posted by in General Dentistry | Comments Off on Nutrition and Inflammation
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