THE ROLE OF

NUTRITION
AND IMMUNE
SYSTEM

DR-Eng. Akhir Pebriansyah, MSc

 DR-Eng Akhir Pebriansyah, SPt, MSc

State Veterinary Institute

 COVID-19 is an emerging, rapidly evolving situation
No disease is more difficult to study than
pandemic virus. It comes, it spreads, it
vanishes with unexampled suddenness.
3/29/2020
14:41:00

Let’s brainstorm to cope up this pandemic until we figure out the definitive treatment ??

:The lesion of Pandemic Science May 1919

 Can we 'boost’
our immune system against
COVID-19?

Source: berbagai sumber, 2020

 COVID 19

 Deadly virus are from bats of Shitov cave

 Especially, COVID 19 has been spread from Wuhan city,

China
 Results in severe acute respiratory syndrome
Immunopathology of COVID-19
Immunomodulatory response of sympathetic nervous system interacting with
immune cells via β2 adreno receptor and Norepinephrine
The sympathetic neurotransmitter norepinephrine modulates the level of T and B lymphocyte activity by
binding to the beta2-adrenergic receptor (beta2AR).

Norepinephrine

Brain Immune
communication
pathway

Cytokines

Sanders VM. The beta2-adrenergic receptor on T and B lymphocytes: do we understand it yet?. Brain Behav Immun. 2012;26(2):195–200. doi:10.1016/j.bbi.2011.08.001

Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000;52(4):595–638.
 Norepinephrine Beta agonist

Immune Cell

Glucose uptake and glycolysis Effector activity Proliferation

β-AR signaling suppresses the initial priming phase of anti-tumor CD8+ T cell-responses, providing a rationale to use clinically available β-blockers in patients to improve cancer
immunotherapies.
Kin NW, Sanders VM. It takes nerve to tell T and B cells what to do. J Leukoc Biol. 2006;79(6):1093–1104. doi:10.1189/jlb.1105625

Qiao G, Bucsek MJ, Winder NM, et al. β-Adrenergic signaling blocks murine CD8+ T-cell metabolic reprogramming during activation: a mechanism for immunosuppression by adrenergic
stress. Cancer Immunol Immunother. 2019;68(1):11–22. doi:10.1007/s00262-018-2243-8
 Norepinephrine (NE) modulates the functions of memory CD8 T cells by inducing
inflammatory cytokine production and reducing activation-induced memory CD8 T cell
expansion.

• Memory CD8 T cells express more beta 2 adrenergic receptors than naïve cells.
• NE treated memory CD8 T cells produce more inflammatory cytokines.
• NE treated memory CD8 T cells produce less growth-related cytokines.
• Memory CD8 T cells from adults with high NE have more inflammatory cytokine expression.

Slota C, Shi A, Chen G, Bevans M, Weng NP. Norepinephrine preferentially modulates memory CD8 T cell function inducing inflammatory cytokine
production and reducing proliferation in response to activation. Brain Behav Immun. 2015;46:168–179. doi:10.1016/j.bbi.2015.01.015
Sympathetic Nerve distribution is extensive in bronchus, bronchiole, pulmonary vessels and
bronchial glands

Green stain : tyrosine hydroxylase.

Grebe, Kristie M., et al. "Cutting edge: sympathetic nervous system increases proinflammatory cytokines
and exacerbates influenza A virus pathogenesis." The journal of immunology 184.2 (2010): 540-544.
 Immune response mediated through β2 Adrenergic receptors via Norepinephrine
is altered in chronic stress situation

T cell T cell

Ortega E, Gálvez I, Martín-Cordero L. Adrenergic Regulation of Macrophage-Mediated Innate/Inflammatory Responses in Obesity and Exercise in this Condition: Role of β2 Adrenergic Receptors. Endocr Metab Immune Disord Drug
Targets. 2019;19(8):1089–1099. doi:10.2174/1871530319666190206124520
CDC. H1N1 flu. http://www.cdc.gov/h1n1flu/. Atlanta, GA. 2009. Obesity is an independent risk factor
Kohm AP, Sanders VM. Norepinephrine and beta 2-adrenergic receptor stimulation regulate CD4+ T and B lymphocyte function in vitro and in vivo. Pharmacol Rev. 2001;53(4):487–525.
Modulation of T helper 1 and T helper 2 immune balance in a stress mouse model during Chlamydia muridarum genital
infectionTesfaye Belay, Elisha Martin, Gezelle Brown, Raenel Crenshaw, Julia Street, Ashleigh Freeman, Shane Musick, Tyler Kinder doi: https://doi.org/10.1101/863753
4
Viral infection and sympathetic hyperactive stage
Viral infection act as stressor “it activate sympathetic nervous system”

Respiratory Virus

SNS

NE

• Dunn AJ, Powell ML, Meitin C, Small PA Jr. Virus infection as a stressor: influenza virus elevates plasma concentrations of corticosterone, and brain concentrations of
MHPG and tryptophan. Physiol Behav. 1989;45(3):591–594. doi:10.1016/0031-9384(89)90078-4
• Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice.Chandler JD, Hu X, Ko EJ, Park S,
Lee YT, Orr M, Fernandes J, Uppal K, Kang SM, Jones DP, Go YM.Am J Physiol Regul Integr Comp Physiol. 2016 Nov 1;311(5):R906-R916. doi:
10.1152/ajpregu.00298.2016. Epub 2016 Aug 24.PMID: 27558316
In pre existing chronic stress condition, viral infection aggravate sympathetic hyperactive state causing
hyperimmune response due to cytokines storm leading to ARDS

Respiratory Virus

Chronic stress condition

NE

Hyperinflammation due to
SNS cytokine storm

Immune cells
 Speculation

➢ Like other respiratory virus, Covid-19 infection activate sympathetic nervous system of body
➢ In chronic stress condition, viral infection dysregulated immune system mediated through increase
Norepinephrine release due to sympathetic hyperactivity via beta 2 adrenoreceptors
➢ Magnitude of Sympathetic hyperactivity determine the outcome during the course of Covid-19 infection.
Hypothesis :1

Beta 2 adrenoreceptors blocker treatment prevent immune dysregulation following Covid-19 infection

β2 Blocker
COVID-19 Propanolol
Nadolol
Labetolol
Sotalol
Pindolol
Carvidilol

SNS

VIRAL CLEARANCE AND

β2AR
RECOVERY

Immune cells
 Hypothesis: 2

2) Alpha 2 agonists prevent further release of NE and prevent sympathetic hyperactivity

and immune dysregulation.

COVID-19

SNS
α2 AGONIST
NE
Dexmedetomidine
Clonidine
Moxonidine

β2AR Erratic immune

response leading to
ARDS
Immune cells
Hypothesis: 3

3) Stellate ganglion blocks prevent sympathetic outflow to ipsilateral lungs and prevent disease
progress and ARDS development in severe disease

Dauber IM, Weil JV. Lung injury edema in dogs. Influence of sympathetic ablation. J Clin Invest.
1983;72(6):1977–1986. doi:10.1172/JCI111162
Other pandemic in the world :
Wabah Athena 430 SM
Wabah Antonine 165-180 M
Wabah Cyprian 250-271 M
Wabah Justinian 541-542 M
Epidemi Cocolitzi 1545-1548
Wabah London 1665-1666
Wabah Besar Marseille 1720-1723
Wabah Rusia 1770-1772
Demam Kuning Philadelphia 1793
Wabah Flu 1889-1890
Wabah Polio US- 1916
Flu Asia 1057-1958

5
 IT’S SAID THAT THESE ARE TURBULENT TIMES, BUT WHEN HAVE TIMES
NOT BEEN TURBULENT?
1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s

1930s 1945-early 1970s 1961 1981 1995 2011

Great Post War boom First Man in Space 1970s IBM Oklahoma City Japanese earthquake
Depression Stagflation launches PC bombing

1939-1943 1953 1962 1991 2001

World War II DNA discovered Cuban Missile Crisis 1972 Watergate Invention of World Terrorists attacks on
9-11 2010
Wide Web Asian Tsunami

1933 1950-53 1989

New Deal starts Korean War 1973 Berlin wall falls 1995-2000
1969
Oil crisis Dot.com bubble 2002
First man on the
Euro introduced
moon

1937 1945
1979 1990
Hindenberg UN founded 2009
1955-75 Operation Desert
disaster Energy crisis Swine Flu
Vietnam war Storm
Possible hypothetical treatment

MODERATE SEVERE
Stellate ganglion block
Incremental dose of IV Dexmedetomidine
Incremental dose of IV labetalol

>60 yrs.
Clonidine oral or patch
30-59 yrs. Moxonidine
Nadolol
13-29 yrs. Propranolol
Labetalol
MILD

Tizanidine

1) Vongpatanasin W, Kario K, Atlas SA, Victor RG. Central sympatholytic drugs. J Clin Hypertens (Greenwich).
2011;13(9):658–661. doi:10.1111/j.1751-7176.2011.00509.x
2) Fenton C, Keating GM, Lyseng-Williamson KA. Moxonidine: a review of its use in essential
hypertension. Drugs. 2006;66(4):477–496. doi:10.2165/00003495-200666040-00006
PUSH CREATIVITY
PUSH CREATIVITY
 UP
NORMAL
NGGAK GINI
JUGA....
 Stress| what we can do

Corticosteron

Imbalance microflora
Metabolic Less performance of the feed
malfunction
(no absorption of amino acids)
Upset vital systems
Mineral excretion More risks of pathogen infections
in the intestines: protein stimulates
E-Coli to grow

Pendekatan Pendekatan Pendekatan

Copyright © 2020 Behn Meyer Group

Genetic Management NUTRISI

Source: Gonzales, 2020

Yang bisa kita covered

38 |
 Stress? | What is the goal
Chelated minerals
for imunity esp. when feed intake (Mishra, 2013)
→ Helps to call hormone corticosterone (Al-Daraji and Amen 2011)
→ Direct bactericidal due to Cu ( Thomas, 2014)

Essential amino acids

Metabolic response and performance improvement (Tabiri, 2001)

→ increase protein digestability and energy to help physiological stress (Leathwood, 1987)

Organic acids

Bacteriostatic and bacterisidal to control

infectious diseases due to stress (Mehdi, 2018)
Copyright © 2020 Behn Meyer Group

Completes the lack of nutrients →

cope the stress
| 39
 IMMUNE HEALTH

 Our immune system not only protect us from infections,

but also has a role in cancer surveillance, brain fuctions, and

aging
 Almost 70% of all immune cells are present in our guts

▪ More immunoglobulins are produced in our gut than anywhere

else in our body
▪ A significant fact of our immune system interact with what we
eat
BACKGROUND A NUTRITION

 NUTRITION → is a science of dealing with the utilization of food by the

body process which transforms food into
body tissue and energy

 Nutrients → can utilized by animals for maintenance, growth, production,

reproduction, health control

 Top 6 nutrients needed → Protein, carbs, fats, minerals, vitamins, water

 Factor can be control → water quality, environmental factor (closed house),

animal factors
 IMMUNONUTRITION

 Untill recently, nutrition was thought to be needed only

to provide the building blocks of the immune system
 However, we now find that is also provides the force for
changing how the body responds to infections, stress,
self reactivity, etc
 Studies are now looking at how these interactions
ultimately affect our immune status
IMMUNONUTRITION
 Macronutrients such as
- protein, carbs and fat
- Provide the structure of immune cells and signals
 Micronutrients such as
- Vitamins and minerals
- Provide activation (or inhibition) signals
 Antioxidants
- Some vitamins, minerals, and co-enzymes
- Chemical which counteract free radicals or reactive oxygen species
which are made by cell during regular metabolism
 Phytochemicals
- Coloring and flavoring plant based
- Have anti-inflammantory , anti oxidant and anti UV effect
 WRAP UP
 Stress can weaken the immune system

 Prolonged stress is unhealthy

 Well nutrition and management is very helpful

to maintenance the immune system

 THANKYOU

Akhir Pebriansyah, PhD

+31626827949
Akhir.Pebriansyah@behnmeyer.co.id

Dr. Brian

TREY
research
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