Inflammation

Inflammation is the manifestation of the body’s
response to tissue injury, whether caused by infection,
physical trauma, chemicals or heat. It is often
considered in terms of acute infl ammation and
chronic infl ammation. The infl ammatory response
is immensely complex and no attempt is made here
to describe it in full. We will focus instead upon the
physiological actions of selected infl ammatory mediators
that have relevance to the immunogenic properties
of certain vitamins (vitamins A, D, E, B6 and C;
see relevant chapters).
5.3.1 The infl ammatory response
The purpose of an infl ammatory response is to bring
fl uid, proteins and cells from the blood into the damaged
tissues, where they effect host defence and repair.
The main events that facilitate this are dilation of
the arterioles to increase blood fl ow to the affected
area; increased permeability of venules, which allows
plasma fl uid to pass through the endothelium; and
migration of leucocytes across venular endothelium
to the site of injury. The classical signs of infl ammation
– redness, heat, swelling and pain – are a direct
result of these events.
The acute vascular response to infection takes place
within seconds of the initial stimulus, and lasts for
some minutes. Mast cells are stimulated to release
preformed molecules from storage granules. Some of
these molecules (e.g. histamine) are vasoactive, while
others are chemotactic. Platelets also release vasoactive
amines, as well as coagulation factors which lead
to localized fi brin deposition.
The acute cellular response takes place over the next
few hours. The fi rst of the phagocytic cells to act are the
resident macrophages already present in the affected
area. When stimulated by products from the infl amed
tissue, these cells enlarge and break away from their attachments,
once again becoming mobile macrophages
with phagocytic activity. Polymorphonuclear phagocytes
(mainly neutrophils) from the bloodstream arrive
on the scene by the controlled process of migration.
In this process, capillary endothelial cells close to
infl ammation sites are induced to produce adhesion
molecules on their luminal surface. The phagocytes
passing through the capillaries also have adhesion
molecules on their surface. Interaction between the
respective adhesion molecules causes the phagocytes
to stick to the endothelium. The phagocytes are then
activated to squeeze between the endothelial cells and
to secrete collagenases and other enzymes in order to
‘digest’ their way through the basal lamina. Having
now reached the tissue, the phagocytes are guided
to the infl ammation zone by chemotactic molecules.
Cells of infl amed tissues increase their synthesis of
heat shock proteins in response to the thermal stress,
despite a decrease in total protein synthesis.
If the infection is suffi ciently severe, a chronic
cellular response may follow over the next few days.
Circulating monocytes arrive and enlarge to become
macrophages. More leucocytes are made available
through mobilization of bone marrow stores. Finally,
after days or weeks, in-growth of fi brous tissue helps
in the healing process.
If the infl ammatory response is unable to destroy
the infectious agent or to completely remove all of
the accumulated products, the affected area is walled
off from the surrounding healthy tissue by granulomatous
tissue. A ball of cells known as a granuloma
is formed when macrophages and lymphocytes, and
later epitheloid cells and giant cells, surround the affected
area.
Infl ammatory diseases such as rheumatoid arthritis
arise because the host’s immune system fails in some
way to regulate the infl ammatory response.
5.3.2 Mediators of the infl ammatory
response
The infl ammatory response is mediated by chemicals
released from cells of the tissue and from cells of the
immune system. An important early phase mediator
is histamine, which is released from the storage granules
of mast cells and also by platelets within seconds
of initiation. Later, about 6–12 hours after initiation,
vascular events are mediated by prostaglandins and
leukotrienes, which are products of arachidonic acid
metabolism. These molecules are newly synthesized
and secreted by a wide variety of cell types in response
to an appropriate stimulus. Cytokines (Section 5.5)
are important in signalling between cells as infl ammatory
reactions develop.
102 Vitamins: their role in the human body
Histamine
Histamine induces relaxation of the smooth muscle
walls of pre-capillary arterioles, causing the vessels
to dilate and thereby increasing blood fl ow; this produces
the redness and heat. Histamine also causes retraction
of endothelial cells in post-capillary venules,
forming intracellular gaps; the resultant increase in
permeability leads to oedema (leakage of plasma into
the interstitial space) and produces the swelling and,
in part, pain. These effects on the blood vessels are
mediated through stimulation of histamine type 1
(H1) receptors.
Histamine also participates in immune suppression
through stimulation of histamine type 2 (H2) receptors
on neutrophils and suppressor T cells (Section
5.6). Thus histamine may have either an amplifying or
an inhibiting effect on the infl ammatory response, depending
upon the stage of infl ammation and whether
H1 or H2 receptors are stimulated.
Excess histamine leads to hypersensitivity and antihistamine
therapy is well known for alleviating conditions
such as hay fever and infl ammatory skin disorders.