Inflammation terrain as cause of chronic illnes

1. Inflammation
Terrain.
Prof.Dr.med. Arturo O’Byrne
Integrative Medicine Professor
Universidad Javeriana. Colombia

2. Objective
• Chronic illness are
immflamatory
processes…
–understand
Inflammation Terrain.

3. Introduction.
• Fundamental to
biological medicine:
–The role of the
microenvironment as…
•Critical supporter
of healthy cells.

4. Bibliographic reference.
• Buttle DJ.
• Factors controlling
matrix turnover in
health and disease.
• Biochem Soc Trans. Aug
2007;35(Pt 4):643-646.

5. Introduction.
• The treatment
could be improved by…
–Stimulation or
optimization of,
•patient’s individual
inflammation
resolution process.

6. Bibliographic reference.
• Serhan CN, Chiang N.
• Endogenous pro-resolving
and anti-inflammatory lipid
mediators: a new
pharmacologic genus.
• Br J Pharmacol.
Mar 2008;153 Suppl 1:S200-215.

7. Bibliographic reference.
• Bannenberg GL.
• Resolvins: Current
understanding and future
potential in the control
of inflammation.
• Curr Opin Drug Discov Devel.
Sep 2009;12(5):644-658.

8. Inflammatory environment.
• Cellular environment
(millieu) in which
inflammation occurs,
influence on the
inflammatory process…
–Critical importance

9. Inflammatory environment.
• Inflammatory reactions
occur within
microenvironments
tissue specific cells:
–Fibroblasts, endothelial cells,
macrophages…
•Specialized ECM components

10. Bibliographic reference.
• Serhan CN, Brain SD,
Buckley CD, et al.
• Resolution of
inflammation: state of the
art, definitions and terms.
• Faseb J. Feb
2007;21(2):325-332.

11. Bibliographic reference.
• Buckley CD.
• Why does chronic
inflammation persist:
An unexpected role
for fibroblasts.
• Immunol Lett.
Jul 2011;138(1):12-14.

12. Inflammatory environment.
• Fibroblasts
–Play an
active role
in chronic
inflammation!!.

13. Inflammatory environment.
• Disordered fibroblast
behavior…
–Can lead to sustained
recruitment,
•Inappropriate
retention of leukocytes.

14. Bibliographic reference.
• Buckley CD, Pilling D, Lord JM,
Akbar AN, Scheel-Toellner D,
Salmon M.
• Fibroblasts regulate the switch
from acute resolving to chronic
persistent inflammation.
• Trends Immunol.
Apr 2001;22(4):199-204.

15. Inflammatory environment.
• First Target: the tissue
microenvironment,
in addition to:
• Second target: the stressor and
infiltrating immune cells
–In treating chronic
inflammation.

16. Inflammatory environment.
• Chronic inflammation is
associated with most age-
related diseases including:
–Alzheimer’s,
–Atherosclerosis,
–Osteoarthritis, cancer.

17. Inflammatory environment.
• Throughout lifetime,
–Regularly encounter
internal and external
antigenic stress,
•which activates
the immune system.

18. Inflammatory environment.
• Throughout lifetime,
–Over time…
–Leads to the
accumulation of
antigenic burden.

19. Bibliographic reference.
• Freund A, Orjalo AV,
Desprez PY, Campisi J.
• Inflammatory networks during
cellular senescence: causes and
consequences.
• Trends Mol Med.
May 2010;16(5):238-246.

20. Inflammatory environment.
• Persistent, low-level
immune activation,
• Increase of the basal
expression of
inflammatory factors…
–can initiate and maintain
substantial chronic
inflammation.

21. Bibliographic reference.
• Vasto S, Candore G,
Balistreri CR, et al.
• Inflammatory networks in
ageing, age-related diseases
and longevity.
• Mech Ageing Dev.
Jan 2007;128(1):83-91.

22. Bibliographic reference.
• Caruso C, Lio D, Cavallone
L, Franceschi C.
• Aging, longevity,
inflammation,
and cancer.
• Ann N Y Acad Sci.
Dec 2004;1028:1-13.

23. Bibliographic reference.
• Franceschi C, Bonafe M,
Valensin S, et al.
• Inflamm-aging. An
evolutionary perspective
on immunosenescence.
• Ann N Y Acad Sci.
Jun 2000;908:244-254.

24. Inflammation / stressors.
• Only when
the stressors
are addressed…
–Can chronic
inflammation
be resolved.

25. Lymphatic / stressors.
• Lymphatic system
that promotes
lymphatic drainage
and cell migration…
–is essential to help
the body to eliminate or
minimize those stressors.

26. ECM and Cells.
• Biological medicine
considers the cell and
its ECM…
–As the collective
functional unit
in higher organisms.
•Not the cell alone.

27. ECM and Cells.
• Communication
between a cell and its
microenvironment
is bidirectional…
–Forms the basis of
the homeodinamic
tissues control.

28. Inflammation / body functions.
• Changes in the
microenvironment,
• Inflammation,
–Significant impact
on many bodily
functions.

29. Inflammation / body functions.
• Changes at the ECM level
can drive systemic chronic
inflammatory disorders:
–Disturbed stem cell
function.
–Promotion of
tumorigenesis.

30. Bibliographic reference.
• Bhatia A, Kumar Y.
• Cancer-immune equilibrium:
questions unanswered.
Cancer Microenviron.
• Aug 2011;4(2):209-217.

31. Bibliographic reference.
• Grivennikov SI, Greten
FR, Karin M.
• Immunity, inflammation,
and cancer.
• Cell. Mar 19
2010;140(6):883-899.

32. Inflammation and ECM.
• The ECM is also
directly involved…
–In the initiation
and resolution
of inflammatory
responses.

33. Bibliographic reference.
• Sorokin L.
• The impact of the
extracellular matrix
on inflammation.
• Nat Rev Immunol. Oct
2010;10(10):712-723.

34. Inflammation and ECM.
• Metabolic waste
products,
• Exogenous particles that
accumulate in the ECM…
–can function as
inflammatory inducers.

35. Inflammation factors.
• Environmental factors:
–Diet,
–Exercise,
–Lifestyle,
•Affect metabolic
pathways

36. Bibliographic reference.
• Turnbaugh PJ, Ley RE, Mahowald
MA, Magrini V, Mardis ER
• An obesity-associated gut
microbiome with increased
capacity for energy harvest.
• Nature. Dec 21
2006;444(7122):1027-1031.

37. Inflammation factors.
• Intestinal
mucosal
permeability.

38. Bibliographic reference.
• Conterno L, Fava F, Viola R,
Tuohy KM.
• Obesity and the gut microbiota:
does up-regulating colonic
fermentation protect against
obesity and metabolic disease?
• Genes Nutr. Aug 2011;6(3):241-
260.

39. Bibliographic reference.
• Cani PD, Amar J,
Iglesias MA, et al.
• Metabolic endotoxemia
initiates obesity and
insulin resistance.
• Diabetes. Jul
2007;56(7):1761-1772.

40. Inflammation factors.
• Intestinal mucosal
permeability.
–Potentially
inducing
mucosal
inflammation

41. Bibliographic reference.
• Cani PD, Neyrinck AM, Fava F, et al.
• Selective increases of bifidobacteria
in gut microflora improve high-fat-
diet-induced diabetes in mice
through a mechanism associated
with endotoxaemia.
• Diabetologia.
Nov 2007;50(11):2374-2383.

42. Bibliographic reference.
• de La Serre CB, Ellis CL, Lee J,
Hartman AL, Rutledge JC,
Raybould HE.
• Propensity to high-fat diet-induced
obesity in rats is associated with
changes in the gut microbiota and
gut inflammation.
• Am J Physiol Gastrointest Liver
Physiol. Aug 2010;299(2):G440-448.

43. Inflammation factors.
• Obesity often
causes physiological
perturbations such as:
–Oxidative stress,
–Chronic systemic
inflammation.

44. Bibliographic reference.
• Conterno L, Fava F, Viola R, Tuohy
KM.
• Obesity and the gut microbiota:
does up-regulating colonic
fermentation protect against
obesity and metabolic disease?
• Genes Nutr. Aug 2011;6(3):241-
260.

45. Inflammation terrain.
• Consideration of the “terrain”
–Targeting the causes
of conditions associated
with chronic inflammation,
•beyond targeting
symptoms.

46. Inflammation terrain.
• Biological complexity of
chronic inflammation,
–The same intervention
could produce
different effects…
•In different patients
•At different times

47. Bibliographic reference.
• Nathan C, Ding A.
• Nonresolving
inflammation.
• Cell. Mar 19 2010;
140 (6): 871-882.

48. Inflammatory patient profile.
• Therapeutic systems
would benefit…
–from the ability
to assess an
inflammatory
patient profile.

49. Inflammatory patient profile.
• Inflammatory
individual profile,
–Help to identify and
locate resolution
blockages and underlying
pathologies.

50. Inflammatory patient profile.
• Clinical history
–Individual evaluation
of causes…
•Individual treatment of
the inflammatory status
in every patient.

51. Inflammatory patient profile.
• The real possibility of
an individual’s
inflammation resolution
over time.

52. Bibliographic reference.
• Nathan C, Ding A.
• Nonresolving
inflammation.
• Cell. Mar 19
2010;140(6):871-882.

53. Living matrix.
• The ECM, intracellular
cytoskeleton and
nuclear matrix,
–Are directly
interconnected through a
chain of commonly
utilized molecules.

54. Bibliographic reference.
• Huang S, Ingber DE.
• A non-genetic basis for cancer
progression and metastasis:
self-organizing attractors
in cell regulatory networks.
• Breast Dis. 2006;26:27-54.

55. ECM as “body terrain”.
• Cellular
Microenvironment
Information Regulation
–Considers the tissue
microenvironment
•The terrain
of the body.

56. Bibliographic reference.
• Genuis SJ.
• What's out there
making us sick?
• J Environ Public Health.
2012;2012:605137.

57. Conclusion.
• Cardinal role of the
microenvironment as
–Cellular information
exchange center positions
•ECM as a point
of intervention.