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

In the paper

“Many chronic inflammatory diseases only become manifested in patients at older ages. Because of the short life expectancy in the past, our ancestors have not suffered from the chronic inflammatory diseases that we know today.”

In the paper

“Thus, the evolutionary time line of the neuroendocrine immune network that is basis of the present theory goes back at least 400 million years (distance to the suggested common ancestor).”

In the paper

“Since these disease sequelae can be found in many animal models of chronic inflammatory diseases with mammals (e.g., monkeys, mice, rats, rabbits, etc.), the evolutionary time line goes back at least 70 million years.”

In the paper

“It has been hypothesized that genes responsible for energy regulation have been positively selected under conditions without chronic inflammation [8, 10].”

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 [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

“Chronic inflammatory diseases can lead to loss of reproduction potential because affected individuals are at strong disadvantage. Such individuals can be excluded or impaired in the competition for food; they can also have low social status in the group and limited choice or availability of sexual partners.”

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

  “In addition, intense, persistent inflammation can inhibit the hypothalamic–pituitary–gonadal axis, leading to impairment of fertility as demonstrated in studies on the effect of chronic inflammatory diseases on fertility despite good medical control [16–20].”

What the sources say

• Not checked yetcites [16] Ostensen M, Almberg K, Koksvik HS (2000) Sex, reproduction, and gynecological disease in young adults with a history of juvenile chronic arthritis. J Rheumatol 27:1783–1787
• Not checked yetcites [17] Silva CA et al (2010) Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea. Rheumatol Int 31(8):1037–1043 source
• Not checked yetcites [18] Villiger PM, Caliezi G, Cottin V, Forger F, Senn A, Ostensen M (2010) Effects of TNF antagonists on sperm characteristics in patients with spondyloarthritis. Ann Rheum Dis 69:1842–1844 source
• Not checked yetcites [19] Soares PM, Borba EF, Bonfa E, Hallak J, Correa AL, Silva CA (2007) Gonad evaluation in male systemic lupus erythematosus. Arthritis Rheum 56:2352–2361 source
• Not checked yetcites [20] Suehiro RM, Borba EF, Bonfa E, Okay TS, Cocuzza M, Soares PM, Silva CA (2008) Testicular Sertoli cell function in male systemic lupus erythematosus. Rheumatology (Oxford) 47:1692–1697 source

In the paper

“Second, the revised theory addresses the mechanisms of essential hypertension since, on the basis of water loss, acute inflammatory diseases can stimulate water retention using a positively selected water retention system (identical to the energy provision system).”

In the paper

“It has been hypothesized that the genes relevant to the etiology of today’s chronic inflammatory diseases have been positively selected for their effects on normal host defense as well as the host response to serious, albeit non-life-threatening, inflammatory episodes in contrast to chronic inflammatory diseases (Table 2) [8].”

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

In the paper

“which is hypothesized to be the basis of essential hypertension (prevalence in adults 22–32%).”

In the paper

“It can be hypothesized that energy considerations can help explain the relatively constant time course of an adaptive immune response in the context of acute infection.”

In the paper

“For the chronic phase of such immune-mediated diseases, the organism would lack positively selected genes, signaling pathways, and networks to be able to stop the chronic disease in a coordinated fashion.”

In the paper

“If a disease is progressive and longstanding (e.g., autoimmunity) and therapies are available to stop lethal emaciation (i.e., immunosuppression), a chronic phase can develop.”

In the paper

“This version defines more precisely the moment of transition from acute inflammatory disease to chronic inflammatory disease as a time in which energy stores become empty (complete energy consumption).”

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

  “The framework of evolutionary biology and neuroendocrine immune energy regulation thus defines the point of transition from acute disease to chronic disease as the time point of complete energy consumption (19–43 days).”

In the paper

“Thus, sickness behavior and energy disturbance would remain and impair the function of the individual. It becomes a perpetuating factor (Table 5).”

In the paper

“It can be hypothesized that networks for more persistent inflammatory diseases do not exist because they have not undergone the pressure of positive selection.”

In the paper

“In considering energy stores available during these responses, it is important to note that storage occurs primarily in fat tissue (12 kg of triglycerides in the body of a contemporary person, 500,000 kJ), as well as in the liver (150 g glycogen, 2.500 kJ) or muscles (300 g glycogen, 5,000 kJ; 6–7 kg muscle protein, 50,000 kJ) [11, 12].”

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

“HLA DR4 (DRB1*04) is a well-known risk factor for rheumatoid arthritis and other chronic autoimmune diseases, but HLA DR4 (DRB1*04) also has a strong negative association with 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

“In this conceptualization, the induction of systemic responses results from an appeal for energy-rich substrates, called the energy appeal reaction [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

“Thus, one can add the “systemic response” to the list of classical etiologic factors of chronic inflammatory diseases (Table 5) [10]. The “systemic response” in itself can be disease perpetuating.”

What the sources say

• 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

“In summary, it seems plausible that specific genes have not been selected or conserved in evolution because of their putative role in chronic inflammatory diseases, either positive or negative. Rather, genes, signaling pathways, and networks operative in symptomatic chronic inflammatory diseases were likely adapted from normal physiology or serious, albeit non-life-threatening, inflammatory”

In the paper

“An acute infectious disease can be self-limiting and involve an innate immune response of 2 to 3 days; the subsequent phase of the adaptive immune response can last approximately 3 to 4 weeks.”

What the sources say

• Not checked yetcites [22] Meyer-Hermann ME, Maini PK (2005) Cutting edge: back to “one-way” germinal centers. J Immunol 174:2489–2493 source
• Not checked yetcites [23] Meyer-Hermann M (2002) A mathematical model for the germinal center morphology and affinity maturation. J Theor Biol 216:273–300 source

In the paper

“Thus, it seems likely that HLA DR4 (DRB1*04) was positively selected to overcome dengue hemorrhagic fever but not to stimulate rheumatoid arthritis and other autoimmune diseases in later life.”

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

“Both the aging process and medically treated chronic inflammatory diseases are accompanied by mild inflammation, a state that one might call low-grade smoldering chronic inflammation [40, 41].”

What the sources say

• Not checked yetcites [40] Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A (2005) Human immunosenescence: is it infectious? Immunol Rev 205:257–268, 257-268 source
• Not checked yetcites [41] Straub RH, Cutolo M, Zietz B, Schölmerich J (2001) The process of aging changes the interplay of the immune, endocrine and nervous systems. Mech Ageing Dev 122:1591–1611 source

In the paper

“Thus, while sickness behavior may have antilipogenic consequences by suppressing insulin secretion, it can also be prolipolytic through activation of the SNS and the HPA axis. It leads to redirection of stored energy to the activated immune system.”

In the paper

“ACTH can stimulate aldosterone as well as cortisol, which also has mineralocorticoid activity [35].”

What the sources say

• Not checked yetcites [35] Hattangady N, Olala L, Bollag WB, Rainey WE (2011) Acute and chronic regulation of aldosterone production. Mol Cell Endocrinol. doi: 10.1016/j.mce.2011.07.034 source

In the paper

“there are obvious signs of volume overload in chronic inflammatory diseases because serum levels of atrial natriuretic factor and NT-brain natriuretic factor are markedly increased in different diseases [49–52].”

What the sources say

• Not checked yetcites [49] Yasuda M, Yasuda D, Tomooka K, Nobunaga M (1993) Plasma concentration of human atrial natriuretic hormone in patients with connective tissue diseases. Clin Rheumatol 12:231–235 source
• Not checked yetcites [50] Straub RH, Hall C, Kramer BK, Elbracht R, Palitzsch KD, Lang B, Schölmerich J (1996) Atrial natriuretic factor and digoxin-like immunoreactive factor in diabetic patients: their interrelation and the influence of the autonomic nervous system. J Clin Endocrinol Metab 81:3385–3389 source
• Not checked yetcites [51] Peters MJ, Welsh P, McInnes IB, Wolbink G, Dijkmans BA, Sattar N, Nurmohamed MT (2010) Tumour necrosis factor alpha blockade reduces circulating N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis: results from a prospective cohort study. Ann Rheum Dis 69:1281–1285 source
• Not checked yetcites [52] Provan S, Angel K, Semb AG, Atar D, Kvien TK (2010) NT-proBNP predicts mortality in patients with rheumatoid arthritis: results from 10-year follow-up of the EURIDISS study. Ann Rheum Dis 69:1946–1950 source

In the paper

“Since no positively selected programs exist for aging [44] and chronic inflammatory diseases [8, 45]”

What the sources say

• Not checked yetcites [44] Kirkwood TB, Austad SN (2000) Why do we age? Nature 408:233–238 source
• 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 [45] Straub RH, Del Rey A, Besedovsky HO (2007) Emerging concepts for the pathogenesis of chronic disabling inflammatory diseases: neuroendocrine-immune interactions and evolutionary biology. In: Ader R (ed) Psychoneuroimmunology. Elsevier, San Diego, pp 217–232 source

In the paper

“In conclusion, the water retention system shows important similarities to the energy provision system, with operation of the two interacting systems subject to positive selection in evolution to overcome serious, albeit non-life-threatening, transient inflammatory episodes (Table 2).”

In the paper

“The key elements of this system are the sympathetic nervous system (SNS) that activates the renin–angiotensin–aldosterone pathway [34], and the hypothalamic–pituitary–adrenal (HPA) axis with ACTH, aldosterone, and cortisol.”

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
• Not checked yetcites [35] Hattangady N, Olala L, Bollag WB, Rainey WE (2011) Acute and chronic regulation of aldosterone production. Mol Cell Endocrinol. doi: 10.1016/j.mce.2011.07.034 source

In the paper

“water loss through skin wounds depends on the surface area and can amount to 0.35 ml/cm2/day (area, 30 × 30 cm2 = 315 ml/day) [28].”

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

In the paper

“It may not be a simple coincidence that the SNS and the HPA axis can redirect energy-rich substrates from energy stores to the activated immune system as well as serve as major water retention systems.”

In the paper

“Today we can say that Selye’s alarm reaction was not “nonspecific” but rather had important physiologic functions as both, a highly specific energy appeal reaction (as described earlier [9, 10]) as well as a specific water retention reaction.”

What the sources say

• Not checked yetcites [36] Selye H (1951) The general adaptation syndrome and the diseases of adaptation. Am J Med 10:549–555 source

In the paper

“The amount of locally formed water can be large (Fig. 1, orange area), but usually water is lost rapidly in the environment of inflamed tissue via outer and inner surfaces (Table 7).”

In the paper

“Indeed, in aging and in chronic inflammatory diseases, both the SNS and the HPA axis are chronically activated [41, 46–48].”

What the sources say

• Not checked yetcites [41] Straub RH, Cutolo M, Zietz B, Schölmerich J (2001) The process of aging changes the interplay of the immune, endocrine and nervous systems. Mech Ageing Dev 122:1591–1611 source
• Not checked yetcites [46] Dekkers JC, Geenen R, Godaert GL, Bijlsma JW, van Doornen LJ (2004) Elevated sympathetic nervous system activity in patients with recently diagnosed rheumatoid arthritis with active disease. Clin Exp Rheumatol 22:63–70
• Not checked yetcites [47] Jessop DS, Harbuz MS (2005) A defect in cortisol production in rheumatoid arthritis: why are we still looking? Rheumatology (Oxford) 44:1097–1100 source
• Not checked yetcites [48] Straub RH, Paimela L, Peltomaa R, Schölmerich J, Leirisalo-Repo M (2002) Inadequately low serum levels of steroid hormones in relation to IL-6 and TNF in untreated patients with early rheumatoid arthritis and reactive arthritis. Arthritis Rheum 46:654–662 source

In the paper

“The induction of systemic responses results from an appeal for energy-rich substrates, called the energy appeal reaction, and for water retention, called the water retention reaction.”

In the paper

“The key feature relates to the production of cytokines of inflammatory cells, their activation of the energy appeal and water retention reaction, and the extent of water loss via inner and outer surfaces.”

In the paper

“NT-brain natriuretic factor decreased with TNF neutralization therapy but increased under therapy with volume retention—inducing glucocorticoids [49, 51].”

What the sources say

• Not checked yetcites [49] Yasuda M, Yasuda D, Tomooka K, Nobunaga M (1993) Plasma concentration of human atrial natriuretic hormone in patients with connective tissue diseases. Clin Rheumatol 12:231–235 source
• Not checked yetcites [51] Peters MJ, Welsh P, McInnes IB, Wolbink G, Dijkmans BA, Sattar N, Nurmohamed MT (2010) Tumour necrosis factor alpha blockade reduces circulating N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis: results from a prospective cohort study. Ann Rheum Dis 69:1281–1285 source