Chronic inflammation

Dr. Dala Daraghmeh

Ph.D pharmacology, Pharm.d
Email: ddaraghmeh@staff.alquds.edu
Definition:

• Inflammation of prolonged duration (weeks, months, years) in which

active inflammation, tissue injury and healing proceed simultaneously
Characteristics of chronic inflammation

• Infiltration by mononuclear cells (macrophages, lymphocytes, and

plasma cells)
• Tissue destruction by the inflammatory cells
• Repair, involving new vessel formation (angiogenesis) and fibrosis.
Chronic inflammation arises in the following
settings
• Progression from acute inflammation, if the acute response can not be resolved,
either because of persistence of the injurious agent or because of interference
with the normal process of tissue healing. Peptic ulcer disease is a typical
example.
• Intracellular infections: like viral infections.
• Persistent microbial infection e.g. mycobacterium
• Prolonged exposure to potentially toxic agent, e.g. silica, or high levels of lipids.
• Autoimmune disease.
Acute on top of chronic inflammation

• Chronic inflammation may coexist with acute inflammation, due to

persistence of the microbe, or due to mediators released from
macrophages and necrotic tissue.
• Neutrophils will coexist with mononuclear cells in the same tissue.
Chronic inflammatory cells and mediators:

Macrophages:
• The main cells in chronic inflammation.
• Widely distributed in the tissues. Called Kupffer cells in the liver, sinus
histiocytes in the lymph nodes and spleen, alveolar macrophages in
the lungs and microglial cells in the CNS.
• Mononuclear phagocytic system: macrophages in the tissues that act
as sentinels for the immune system.
Macrophages:

• Derived from blood monocytes, where they begin to emigrate within

the first 24-48 hrs after the onset of acute inflammation.
• They are transformed into big cells which are capable of
phagocytosis.
Macrophages:
• At the site of inflammation, under the influence of interferon-γ,
endotoxins, ECM like fibronectin and other products, they are
activated; they increase in size, with eosinophilic cytoplasm, so they
are called “epithelioid macrophages”.
• At the site of inflammation, under the influence of IL-4 or INF-gamma,
several cells may fuse to give “multinucleated giant cells”.
The effect of macrophages in inflammation
Tissue injury
• Acid and neutral proteases, as well as plasminogen activator.
• Complement component and coagulation factors.
• Reactive oxygen species and NO
• AA metabolites
• Cytokines
The effect of macrophages in inflammation
• fibrosis:
• growth factors: PDGF, FGF, TGF beta
• firogenic cytokines
• angiogenesis factors
Macrophages in chronic inflammation
Macrophages in acute inflammtion
• Macrophages can engulf excess
fluid, apoptotic neutrophils and
debris resulting from acute
inflammation, thus participating
in resolution of acute
inflammation.
Lymphocytes:
• They are mobilized in the sitting of any specific stimulus (infection), or
in non-immune stimulus like in infarction or tissue trauma.
• T-lymphocytes: they have a reciprocal relation with the number of
macrophages involved in the chronic inflammation.
• B-lymphocytes: they are the cells responsible for the production of
antibodies through the differentiation into plasma cells.
T-Lymphocytes:
Eosinophils:
• found in inflammation induced by parasitic infections or in allergic
reactions involving IgE, Type I hypersensitivity reactions.
• Eotoxin is a specific chemokine for eaosinophils.
• MBP is a protein found in the granules of eosinophils.
• It is toxic to parasites and causes tissue damage.
Mast cells:
• widely distributed in tissues, especially around blood vessels.
• Has IgE receptors, and so it is important in allergic reactions and in
anaphylactic shock.
• They are the primary source of histamine, mediating acute
inflammation, and cytokines like TNF participating in chronic
inflammation.
Granulomatous inflammation:

• A distinctive pattern of chronic inflammation.

• defined as aggregates of activated macrophages that assume an
epithelial or squamoid-like appearance (epithelioid macrophages).
• Seen in few pathological conditions, so once identified, the
differential diagnosis is limited.
Granulomatous inflammation:

Infectious

Non-infectious
Granulomatous inflammation:
Granulomatous inflammation:
• Aggregates of epithelioid
histiocytes, MNG and central
necrosis.

• Higher power to show the MNG

and the central necrosis.
Granulomatous inflammation:
• Importance: important defense mechanism aiming at either
eradication of the causative microorganism, or “walling off” of the
particles that are resistant to killing and degradation, thus preventing
their spread.
The other defense lines:
• The lymphatics, lymph nodes and mononuclear phagocyte system
form the secondary defense lines.
• During inflammation, lymphatics help in draining edema fluid
together with leukocytes, debris and micro-organisms into the lymph
nodes, resulting in lymphangitis and lymphadenitis.
The other defense lines:
• Bacteremia develops if the micro-organisms failed to be contained
within the lymph nodes and gain access into the blood stream.
• The phagocytic cells in the liver, spleen and bone marrow constitute
the third defense line.
The other defence lines
• Failure of containment of the micro-organism leads to seeding of
distant sites. Heart valves “endocarditis”, meninges “meningitis”,
kidney “renal abscesses”, and joints “arthritis” are the favored sites.
Morphologic patterns of inflammation:
• 1.Serous inflammation:
• Outpouring of a watery,
relatively protein free fluid,
either from the serum or
the mesothelial covered
spaces “effusion”.
• Resolution is the outcome.
2.Fibrinous inflammation:

§ Exudation of fibrinogen, due to

vascular permeability.
§ Appears as an eosinophilic
meshwork of threads or coagulum.
§ Either complete resolution is
degraded by fibrinolysis.
Organization with growth of blood
vessels and fibroblasts may occur.
Morphologic patterns of inflammation:
• Suppurative “purulent” inflammation:
• Pus: large amounts of neutrophils, necrotic cells and edema fluid.
• Abscess: focal collection of pus, with central area of necrosis and a
surrounding zone of dilated vessels and fibroblastic reaction.
• Pyogenic micro-organisms: M.O that are more likely to induce a
localized suppurative inflammation e.g. Staphylococcus.
• Healing is always by scarring and fibrosis.
3.Suppurative “purulent” inflammation:
• Pus: large amounts of neutrophils, necrotic cells
and edema fluid.
• Abscess: focal collection of pus, with central
area of necrosis and a surrounding zone of
dilated vessels and fibroblastic reaction.
• Pyogenic micro-organisms: M.O that are more
likely to induce a localized suppurative
inflammation e.g. Staphylococcus.
• Healing is always by scarring and fibrosis.
4.Ulceration:
• A site of inflammation where the
epithelial surface is necrotic and
eroded.
• Caused by toxic or traumatic injury to
the epithelium or due to vascular
compromise.
• Has 3 layers: neutrophilic exudates,
vascular proliferation, and fibroblastic
proliferating layer.
• Resolution or fibrosis.
Morphologic patterns of inflammation: