Download obstructive sleep Apnea and the immune system

Obstructive Sleep Apnea and the Immune System
By Mohammed Quadri, RPSGT
Sleep disturbances affect practically every segPhysical barriers prevent pathogens such as
ment of society permeating across all ethnic, sobacteria and viruses from entering the organism.
cio-economic and age groups. Obstructive sleep
If a pathogen breaches these barriers, the innate
apnea is a process with gradual onset, many
(natural) immune system provides an immeditimes starting with habitual snoring. Obstructive
ate, but non-specific response. When diseaseapneas are characterized by partial or complete
producing microorganisms overcome the natural
airway obstruction during sleep, reductions in
immune system, the adaptive immune system is
blood oxygen levels, severe sleep fragmentation
activated.
and excessive daytime sleepiness. Left untreated,
The immune system develops a specific
sleep apnea leads to a progression in upper
response to specific intruders. This specific
MOHAMMED QUADRI,
airway inflammation and may lead to various
response is more effective and has a memory
RPSGT
other complications such as depression, fatigue,
response that helps it quickly fight against simihypertension, sleep deprivation, drowsy driving, arrhythmias,
lar infections in the future. Immunity results when antigens
stroke and even sudden death.1
that are present on the surface of an invader stimulate the
The obstructive sleep apnea syndrome is the clinical
production of antibodies. There are two types of immune
consequence of frequent episodes of apnea during sleep.
response: antibody mediated, also know as humoral, which
Obstructive apneas are pauses in breathing that last at least
is regulated by B cells; and cell mediated, which is controlled
10 seconds and are accompanied by physical attempts to
by T cells.
breathe. Usually patients with 15 or more episodes of apnea
T cells are lymphocytes that migrate to the thymus (i.e., a
per hour of sleep are considered to have moderate to severe
gland at the base of the neck) and are associated with lymph
sleep apnea. Although prevalence estimates vary, obstructive
nodes and spleen. B cells are in the bone marrow and are
sleep apnea affects at least two percent to four percent of
responsible for antibody response. Antibodies are a type of
middle-aged adults in the general population.2
protein molecule known as an “immunoglobulin”; there are
five classes of immunoglobulins: A,G,E,D and M.
The Immune System
Inflammation is one of the first responses of the immune
The immune system protects organisms from infection and
system to infection.3 The symptoms of inflammation are redinjury with specific defenses that are known as host defense
ness and swelling, which are caused by increased blood flow
mechanisms. These host defense mechanisms can be categoto the tissue. Inflammation is produced by eicosanoids (sigrized in the following groups:
naling molecules) and cytokines (regulatory proteins), which
are released by injured or infected cells. Eicosanoids include
Physical and Chemical Barriers
prostaglandins that produce fever and the dilation of blood
 Morphologic integrity of skin
vessels associated with inflammation, and leukotrienes that
 Sphincters (muscles that open and close a body
attract certain white blood cells (leukocytes).4,5 Common cyopening)
tokines include interleukins that are responsible for commu Epiglottis (cartilage that covers the windpipe while
nication between white blood cells; chemokines that promote
swallowing)
chemotaxis (movement toward or away from a stimulus); and
 Normal secretory and excretory flow
interferons that have anti-viral effects, such as shutting down
 Endogenous microbial flora (“normal” bacteria)
protein synthesis in the host cell.6 Growth factors and cyto Gastric acidity
toxic factors also may be released. These cytokines and other
Inflammatory Response
chemicals recruit immune cells to the site of infection and
 Circulating phagocytes (white blood cells that break
promote healing of any damaged tissue following the removal
down bacteria)
of pathogens.7
 Complement (a system of proteins that helps destroy
Sleep Apnea & the Immune System
bacteria)
Some research suggests that inflammation, particularly
 Other humoral (body fluid) mediators
mucosal
inflammation, could partially underlie sleep apnea.
(e.g., bradykinin)
Supporting this claim is the fact that when sleep apnea is
Reticuloendothelial System
treated with continuous positive airway pressure (CPAP),
 Tissue phagocytes
inflammation is reduced. In addition, inflammatory mediators appear to play a role in both leading to injury of sensory
Immune Response
motor nerves in the upper airway and impairing muscle
 T lymphocytes (cells that promote cellular immunity)
contraction, contributing to upper airway muscle dysfunction
and their soluble products
in sleep apnea. Moreover, surrogate biomarkers such as nitric
 B lymphocytes (cells that promote
oxide have established that nasal and oropharyngeal mucosal
humoral immunity) and immunoglobulins
inflammation is present in patients with sleep apnea.8,9
Obstructive sleep apnea holds promise as a model for
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A2Zzz 2008
• volume 17 • number 4
studying sleep and cytokines because of its many relevant
characteristics, including neuroimmune interactions, mood
changes and behaviors that directly affect the course of the
disorder.10 Main features of pulmonary pathologies (e.g.,
interstitial lung disease, pulmonary hypertension) appear to
be immune activation and vascular endothelial cell injury.
Also interstitial and alveolar inflammation appear to be associated with these pathologies.11 It is important to note that
cytokine-mediated upregulation of the inducible isoform of
nitric oxide snythase, leading to the production of large quantities of nitric oxide, accompanies the immune-inflammatory
processes. Excess nitric oxide generation appears to apply
strong proinflammatory and cytotoxic properties and may be
related to the pathogenesis of autoimmune diseases.12
In a study conducted in Turkey it has been shown that the
levels of circulating inflammatory cytokines interleukin-6
(IL-6) and tumor necrosis factor-alpha (TNF-alpha) are increased in patients with sleep apnea; this increases mortality
in patients with cardiovascular risk factors.13
Findings from several studies have provided evidence for a
link between sleep and immune-related factors, particularly
with regard to the regulation of sleep. For example, experimental challenge tests have shown that bacterial products
and particular immunomodulators may alter the amount of
sleep and its stages.14,15
Detection of immune cell signaling factors in the circulation, such as IL-1 beta, TNF-alpha or its receptor, and/or IL-6,
have been reported in patients with narcolepsy and sleep
apnea who are affected by excessive daytime sleepiness.16
It is still speculative how sleep deprivation may perpetuate disease processes in humans. Sleep deprivation leads
to activation of the immune system, but there is not enough
response to eradicate invading bacteria and toxins, suggesting competing anti-inflammatory processes.17
Conclusion
Evidence continues to mount that sleep disorders lead to
various metabolic disorders; some studies have even shown
that the response to vaccination is much diminished in sleepdeprived people. Sleep disorders may be related to changes
in immune response, suggesting that sleep hygiene and treatment of sleep disorders could improve the body’s response
in fighting infection. Further research is required to find the
genetic link between sleep disorders and immune disorders,
which could lead to the development of novel treatment options for some commonly prevailing, chronic conditions.
The author thanks Susan Zafarlotfi, PhD, and Hormoz
Ashtyani, MD, for their assistance in developing this article.
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Mohammed Quadri, RPSGT, is a foreign medical graduate
who has been in the sleep field for three years. He is Project
Coordinator Clinical Trials at Hackensack University Medical
Center in Hackensack, N.J.
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• volume 17 • number 4
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