Evolutionary medicine and chronic inflammatory state—known and new concepts in pathophysiology

In the paper

“Depending on the amount of stored energy, this time point can be calculated to be 19–43 days.”

• Also stated in: § From acute to chronic inflammatory disease—where is the boundary? · hedged

  “Under conditions of sickness behavior and anorexia without uptake of energy-rich substrates but an increased sickness-related metabolic rate (Tables 1 and 6), the total amount of stored energy would only last for 19 to 43 days in females and 28 to 41 days in males (Table 6).”

What the sources say

• Not checked yetcites [11] Rolfe DF, Brown GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77:731–758 source
• Not checked yetcites [12] Blaxter K (1989) Energy metabolism in animals and man. Cambridge University Press, Cambridge

In the paper

“The number is relatively similar for domestic fowl which have an evolutionary distance to Homo sapiens of 300 million years (Table 6).”

In the paper

“HLA DR4 (DRB1*04) homozygous individuals are 12 times less likely to develop dengue hemorrhagic fever [21].”

What the sources say

• Not checked yetcites [21] LaFleur C et al (2002) HLA-DR antigen frequencies in Mexican patients with dengue virus infection: HLA-DR4 as a possible genetic resistance factor for dengue hemorrhagic fever. Hum Immunol 63:1039–1044 source

In the paper

“According to this theory, disease sequelae can be explained based on redirection of energy-rich fuels from storage organs to the activated immune system.”

• Also stated in: § The framework of evolutionary biology and neuroendocrine immune energy regulation in pathophysiology of chronic inflammatory diseases · plain

  “As a common denominator, the redirection of energy-rich fuels from energy stores to the activated immune system can explain systemic disease sequelae [9].”

What the sources say

• Not checked yetcites [9] Straub RH, Cutolo M, Buttgereit F, Pongratz G (2010) Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med 267:543–560 source

In the paper

“In other words, an acute consuming infectious disease that uses all energy stores can only last until the stores are empty, say 19 to 43 days.”

In the paper

“Due to the physical restrictions of energy storage under natural paleolithic conditions, an acute infectious disease may not last much longer than 3 to 6 weeks.”

In the paper

“On the basis of these considerations, typical disease-related sequelae that are very common in chronic inflammatory diseases have been linked to transient inflammatory episodes [9, 10]. Here, these sequelae have an important function in supporting the transiently activated immune system and tissue inflammation (Table 4).”

What the sources say

• Not checked yetcites [9] Straub RH, Cutolo M, Buttgereit F, Pongratz G (2010) Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med 267:543–560 source
• Not checked yetcites [10] Straub RH (2011) Concepts of evolutionary medicine and energy regulation contribute to the etiology of systemic chronic inflammatory diseases. Brain Behav Immun 25:1–5 source

In the paper

“Antagonistic pleiotropy can explain why genes positively selected at younger ages can have disease-supporting roles in later life independent of the selection process.”

In the paper

“Since uptake of energy-rich substrates has an upper threshold of 20,000 kJ per day (the absorptive capacity in the gut) [11, 12], it is important for the organism to partition energy-rich substrates according to fine-tuned mechanisms of energy regulation.”

What the sources say

• Not checked yetcites [11] Rolfe DF, Brown GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77:731–758 source
• Not checked yetcites [12] Blaxter K (1989) Energy metabolism in animals and man. Cambridge University Press, Cambridge

In the paper

“In this regard, the point can represent a range in time because the consumption curve depends on stored energy reserves (Table 6).”

In the paper

“To explain these seemingly disparate observations, it can be proposed that sickness behavior represents an element of an adaptive program that has been positively selected for transient immune and inflammatory reactions to limit energy utilization for such activities as foraging and courtship behavior [8, 26, 27].”

What the sources say

• Not checked yetcites [8] Straub RH, Besedovsky HO (2003) Integrated evolutionary, immunological, and neuroendocrine framework for the pathogenesis of chronic disabling inflammatory diseases. FASEB J 17:2176–2183 source
• Not checked yetcites [26] Dantzer R, Kelley KW (2007) Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 21:153–160 source
• Not checked yetcites [27] Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56 source

In the paper

“In this scenario, the energy appeal reaction has been positively selected for transient inflammatory episodes.”

In the paper

“These considerations thus suggest that the time point of total energy consumption marks the upper threshold of an acute disease period for which genes, signaling pathways, and networks can be subject to positive selection.”

In the paper

“If an acute inflammatory response lasted longer than the time point at which energy stores were exhausted, the affected person would probably have died due to inanition and starvation, preventing transfer of genes to any offspring.”

In the paper

“However, prolonged operation of these adaptive programs such as in chronic inflammatory diseases of today can in itself become pathogenic.”

In the paper

“To meet the challenges of infection and other environmental stress, an activated immune system has an urgent need for energy-rich substrates that must be allocated from internal and external energy stores (glycogen, proteins, triglycerides, or free fatty acids) [9].”

What the sources say

• Not checked yetcites [9] Straub RH, Cutolo M, Buttgereit F, Pongratz G (2010) Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med 267:543–560 source

In the paper

“The response of the adaptive immune system with a maximum of proliferation until days 12 to 14 and subsequent contraction until days 21 to 28 is surprisingly constant in various acute infectious diseases [24].”

What the sources say

• Not checked yetcites [24] Murphy KM, Travers P, Walport M (2011) Janeway’s immunobiology. Taylor & Francis, Oxford

In the paper

“Studies in a number of systems have demonstrated that circadian rhythms of neuronal, endocrine, and immune systems can regulate energy metabolism and partition fuels to daytime and nighttime consumers [9, 13–15].”

What the sources say

• Not checked yetcites [9] Straub RH, Cutolo M, Buttgereit F, Pongratz G (2010) Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med 267:543–560 source
• Not checked yetcites [13] Le Magnen J (1988) Lipogenesis, lipolysis and feeding rhythms. Ann Endocrinol (Paris) 49:98–104
• Not checked yetcites [14] Lange T, Dimitrov S, Fehm HL, Westermann J, Born J (2006) Shift of monocyte function toward cellular immunity during sleep. Arch Intern Med 166:1695–1700 source
• Not checked yetcites [15] Lange T, Dimitrov S, Bollinger T, Diekelmann S, Born J (2011) Sleep after vaccination boosts immunological memory. J Immunol 187:283–290 source

In the paper

“In chronic smoldering inflammation, however, there is no increased water loss. In contrast, there is increased water generation in inflamed tissue and inflammatory cells, and the activation of the water retention system persists. This combination leads to a net increase of the systemic fluid volume”

In the paper

“Acute inflammatory episodes require abundant energy and are often accompanied by local and systemic water loss (Table 7).”

What the sources say

• Not checked yetcites [28] Davies JW, Lamke LO, Liljedahl SO (1974) A guide to the rate of non-renal water loss from patients with burns. Br J Plast Surg 27:325–329 source
• Not checked yetcites [29] Jacob M, Chappell D, Hofmann-Kiefer K, Conzen P, Peter K, Rehm M (2007) Determinants of insensible fluid loss. Perspiration, protein shift and endothelial glycocalyx. Anaesthesist 56:747–758, 760–764 source

In the paper

“the overall stimulus might be strong enough to induce a mild systemic water retention and energy appeal reaction (responses shown for low IL-6 serum concentrations in ref. [42, 43]).”

What the sources say

• Not checked yetcites [42] Tsigos C, Papanicolaou DA, Defensor R, Mitsiadis CS, Kyrou I, Chrousos GP (1997) Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure. Neuroendocrinology 66:54–62 source
• Not checked yetcites [43] Tsigos C, Papanicolaou DA, Kyrou I, Raptis SA, Chrousos GP (1999) Dose-dependent effects of recombinant human interleukin-6 on the pituitary-testicular axis. J Interferon Cytokine Res 19:1271–1276 source

In the paper

“many metabolic reactions that degrade storage forms of energy-rich substrates need water for hydrolysis (Fig. 1) [30–32].”

What the sources say

• Not checked yetcites [30] Berg JM, Tymoczko JL, Stryer L (2002) Biochemistry. Freeman, New York
• Not checked yetcites [31] Michal G (1999) Biochemical pathways. Spektrum Akademischer Verlag, Heidelberg
• Not checked yetcites [32] Rassow J, Hauser K, Netzker R, Deutzmann R (2008) Biochemistry. Georg Thieme, Stuttgart

In the paper

“Under normal conditions in adults, insensible perspiration through skin and respiratory tract can reach 0.5 ml/kg/h (example, 80 kg and 24 h = 960 ml/day) [29].”

What the sources say

• Not checked yetcites [29] Jacob M, Chappell D, Hofmann-Kiefer K, Conzen P, Peter K, Rehm M (2007) Determinants of insensible fluid loss. Perspiration, protein shift and endothelial glycocalyx. Anaesthesist 56:747–758, 760–764 source

In the paper

“due to low-grade inflammation without fever and due to a lack of inflamed exposed surface areas, water is not lost from the system and from inflamed tissue. Water can recirculate between activated immune cells and the system.”

In the paper

“genes, signaling pathways, and networks that are operative in this setting are similar to those that determine acute episodes of inflammation (Table 2).”

In the paper

“During transient inflammatory episodes, due to sickness behavior and anorexia, lipogenic insulin most probably plays a minor role because insulin secretion activated by the presence of carbohydrates would be downregulated.”

In the paper

“degradation of muscle protein needs particularly many molecules of water (Fig. 1, brown area in right upper corner) [31].”

What the sources say

• Not checked yetcites [31] Michal G (1999) Biochemical pathways. Spektrum Akademischer Verlag, Heidelberg

In the paper

“Since the local inflammatory process leads to water loss over local surfaces, locally formed water—by degradation of energy-rich fuels in activated inflammatory cells (Fig. 1, orange area)—can be rapidly lost via the exposed surface (Fig. 2a).”

In the paper

“Thus, important differences exist for water loss from the system and the generation of water from locally inflamed tissue.”

In the paper

“Chronic inflammation accompanied by essential hypertension is a necessary consequence”

In the paper

“These numbers show that loss of water can be quite high during acute inflammatory episodes.”

In the paper

“water retention hormones such as angiotensin II have proinflammatory activities [37].”

What the sources say

• Not checked yetcites [37] Dorffel Y, Latsch C, Stuhlmuller B, Schreiber S, Scholze S, Burmester GR, Scholze J (1999) Preactivated peripheral blood monocytes in patients with essential hypertension. Hypertension 34:113–117 source

In the paper

“Under conditions of local inflammation with exposed outer and inner surfaces, circulating cytokines from inflamed tissue activate the energy appeal and water retention reaction.”

In the paper

“During surgical intervention, which is a model of mild acute inflammatory activation, water loss by insensible perspiration can amount to 1 ml/kg/h (example, 80 kg and 24 h = 1,820 ml/day) [29].”

What the sources say

• Not checked yetcites [29] Jacob M, Chappell D, Hofmann-Kiefer K, Conzen P, Peter K, Rehm M (2007) Determinants of insensible fluid loss. Perspiration, protein shift and endothelial glycocalyx. Anaesthesist 56:747–758, 760–764 source

In the paper

“In these settings, circulating cytokine levels can be 5 to 10 times higher than normal (e.g., IL-6 from 2 pg/ml to 10–20 pg/ml), and the overall stimulus might be strong enough to induce a mild systemic water retention and energy appeal reaction (responses shown for low IL-6 serum concentrations in ref. [42, 43]).”

What the sources say

• Not checked yetcites [42] Tsigos C, Papanicolaou DA, Defensor R, Mitsiadis CS, Kyrou I, Chrousos GP (1997) Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure. Neuroendocrinology 66:54–62 source
• Not checked yetcites [43] Tsigos C, Papanicolaou DA, Kyrou I, Raptis SA, Chrousos GP (1999) Dose-dependent effects of recombinant human interleukin-6 on the pituitary-testicular axis. J Interferon Cytokine Res 19:1271–1276 source

In the paper

“Water is formed when glucose, amino acids, and free fatty acids undergo degradation in the Krebs cycle and during oxidative phosphorylation; these processes occur in the mitochondria of activated cells in inflamed tissue (Fig. 1, orange area).”

In the paper

“the breakdown of one molecule of glucose from glycogen needs two molecules of water (Fig. 1, pink area in left upper corner)”

What the sources say

• Not checked yetcites [31] Michal G (1999) Biochemical pathways. Spektrum Akademischer Verlag, Heidelberg

In the paper

“systemic hypertension could result from the continuous activation of a water retention and energy appeal reaction but without the usual water loss (Fig. 2b).”

In the paper

“the generation of the Cori cycle between the lactate-producing inflamed tissue and the glucose-producing liver [33], involving gluconeogenesis, needs five molecules of water to reactivate one molecule of lactate (Fig. 1, red lines with arrows) [31].”

What the sources say

• Not checked yetcites [31] Michal G (1999) Biochemical pathways. Spektrum Akademischer Verlag, Heidelberg
• Not checked yetcites [33] Tredget EE, Yu YM (1992) The metabolic effects of thermal injury. World J Surg 16:68–79 source

In the paper

“triglyceride breakdown needs three molecules of water for three molecules of free fatty acids (Fig. 1, pink and yellow area on the left side)”

What the sources say

• Not checked yetcites [31] Michal G (1999) Biochemical pathways. Spektrum Akademischer Verlag, Heidelberg

In the paper

“Inhibition of the renin–angiotensin–aldosterone system by angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists exert anti-inflammatory effects as summarized elsewhere [39].”

What the sources say

• Not checked yetcites [39] Boos CJ, Lip GY (2006) Is hypertension an inflammatory process? Curr Pharm Des 12:1623–1635 source

In the paper

“the operation of a proper adaptive immune response with proliferation of B cells and T cells and proliferation of innate immune cells (neutrophils, monocytes) in primary and secondary lymphoid organs needs enormous amounts of water (Fig. 1, green area in left lower corner) [31].”

What the sources say

• Not checked yetcites [31] Michal G (1999) Biochemical pathways. Spektrum Akademischer Verlag, Heidelberg

In the paper

“In the acute situation, water is lost from the system and from inflamed tissue via outer and inner surfaces. The water fluxes are in a balance.”

In the paper

“To overcome systemic water loss during acute inflammatory episodes and events such as trauma, hemorrhage, and burns, a water retention system is activated.”

What the sources say

• Not checked yetcites [34] Bader M, Ganten D (2000) Regulation of renin: new evidence from cultured cells and genetically modified mice. J Mol Med (Berl) 78:130–139 source

In the paper

“In the setting of acute inflammatory episodes such as infectious disease, it is important that the energy appeal reaction and the water retention reaction support the proinflammatory process to eliminate the infectious agent.”

In the paper

“Angiotensin II uses the important proinflammatory signaling cascade of NF-κB activation similar as TNF [38].”

What the sources say

• Not checked yetcites [38] Phillips MI, Kagiyama S (2002) Angiotensin II as a pro-inflammatory mediator. Curr Opin Investig Drugs 3:569–577

In the paper

“If amino acids are completely degraded within the urea cycle in the liver, one molecule of water is needed for one molecule of amino acid (Fig. 1, pink area in the left upper corner).”

What the sources say

• Not checked yetcites [31] Michal G (1999) Biochemical pathways. Spektrum Akademischer Verlag, Heidelberg

In the paper

“The revised version of the theory predicts that the operation of these mechanisms will not depend on the site of inflammation and whether it occurs in arteries, kidneys, gastrointestinal tract, joints, or at various tissues with inflammatory cells.”

In the paper

“the energy appeal reaction and water retention reaction appear to be the result of selection in evolution for their role in transient inflammatory episodes.”

• Also stated in: § Conclusions · plain

  “The revised theory states that energy appeal and water retention reaction have been positively selected for transient inflammatory episodes”

In the paper

“The magnitude of these changes would determine any detrimental effect on the induction of hypertension.”

In the paper

“prolonged operation of these adaptive programs such as in chronic inflammatory diseases of today can in itself become pathogenic because there is no program to counteract continuous water retention and energy appeal reaction during long-term age-related inflammation and in chronic inflammatory diseases.”

• Also stated in: § Conclusions · plain

  “prolonged use of these adaptive programs can in itself become pathogenic.”

In the paper

“Induction of energy appeal reaction and water retention reaction provide a survival value if used for a short period of time.”

In the paper

“these features can now be unified in terms of a redirection of energy-rich fuels from energy stores to the activated immune system and activation of the water retention system.”