IMM2022 Study Guide - Final Guide: Proinflammatory Cytokine, Acute-Phase Protein, Neuroinflammation
4 May 2018
School
Department
Course
Professor
Mental health
Neuropsychological disorders have high DALYs
MDD = major depression (more than two
weeks)
BIPOLAR = periods of mania and depression
DYSTHYMIC DISORDER = MDD symptoms but
less severe, laster more than 2 years
EVIDENCE OF THE IMMUNE SYSTEM IN
MENTAL HEALTH
• Increased pro-inflamm cytokines in
patients
• Decreased No. and function of NKC in
patients
• Shifts in Th1:Th2 ratios
Evidence for the involvement of the
microbiota, as shown in mice. Mice with
dysbiosis have social dysfunction and anxiety.
SCID mice have social deficits.
PRO-INFLAMMATORY CYTOKINES and
depression
IL-1 (a and B) are produced by macrophages
and epithelial cells. Cause fever, inflammation
and T cell activation. Activate macrophages.
Role in AutoIMM and lymphoma.
High levels of IL-6 which is produced by T
cells, macrophages and endothelial cells in the
BBB (can get into the brain). Cause fever, T
and B growth and neutrophil attraction. IL-6
has a role in autIMM eg RA and SLE
High levels of TNF-a which is produced by
macrophages, NKC and T cells. Causes
inflammation through acute phase protein.
Activated the HPA axis. Cause NF-kB
activation and upregulates adhesion
molecules on endothelium increased
neutrophil recruitment. TNFa has a role in
cancer and IDB.
The HPA axis (hypothalamus pituitary
adrenal glands) eg ACTH acts on adrenal
glands secretion of cortisol can lead to
insomnia.
IL-8 is proinflammatory.
NF-kB inflammation causes damage
Note that when cytokines are given as part of
treatment eg IFNa for leukemia see
increased onset of depression.
Cytokines can pass the BBB. IL-6, TNFa and IL-
1B make the BBB leaky. Mastrocytes,
microglia and neurons can produce cytokines.
Factors such as stress, sleep deprivation and
obesity increase the amount of pro-
inflammatory cytokines.
The diet plays a role in mental health both
in decreasing risk of obesity and effects on the
microbiota. Also affects tryptophan
availability. The diet could be a potential
treatment (low No. of participants in studies
findings not yet conclusive)
TRYPTOPHAN EFFECTS
Pro-inflammatory cytokines increase IDO
which pushes tryptophan down the kynuerine
pathway rather than conversion into
serotonin.
Serotonin increases mood and cognition.
Kynuerine produces:
• 3OH-KYM oxidative stress
• QUIN neurotoxic and
neurodegenerative
Cytokines can impair neuroplasticity by
neurotoxicity. Affect the hippocampus – has a
role in learning and memory.
Normally we have healthy neuroinflammation
that is homeostatic and for in the case of
infection
• Homeostatic release of cytokines
and phagocytosis for microbe
elimination, neuroprotection, repair
and regeneration
• Anti-inflammatory termination of
inflammation
In the presence of neurotoxins
inflammation is maladaptive (not good)
Document Summary
Mdd = major depression (more than two weeks) Dysthymic disorder = mdd symptoms but less severe, laster more than 2 years. Increased pro-inflamm cytokines in patients: decreased no. and function of nkc in patients, shifts in th1:th2 ratios. Evidence for the involvement of the microbiota, as shown in mice. Mice with dysbiosis have social dysfunction and anxiety. Il-1 (a and b) are produced by macrophages and epithelial cells. High levels of il-6 which is produced by t cells, macrophages and endothelial cells in the. Cause fever, t and b growth and neutrophil attraction. Il-6 has a role in autimm eg ra and sle. High levels of tnf-a which is produced by macrophages, nkc and t cells. Cause nf-kb activation and upregulates adhesion molecules on endothelium increased neutrophil recruitment. Tnfa has a role in cancer and idb. The hpa axis (hypothalamus pituitary adrenal glands) eg acth acts on adrenal glands secretion of cortisol can lead to insomnia.
