inflammatory response

Inflammation is a signal-mediated response to cellular insult by infectious agents, toxins, and physical stresses. While acute inflammation is important to the immune response, chronic inappropriate inflammation can cause tissue destruction (autoimmunity, neurodegenerative, cardiovascular disease).

acute phase : agents : cytokines : events : pro-inflammatory cytokines : sequence : signs/symptoms

Symptoms & Signs: Inflammation is variably accompanied by fever (pyrogenesis), redness (rubor), swelling (turgor), pain (dolor), and tissue/organ dysfunction (functio laesa).

The sequence of inflammatory events is:
● insult by trauma or pathogenacute phase reaction
_ ● platelet adhesion, vasoconstriction of efferent vessels
_cytokine induced afferent vascular dilatation (vasodilation causing increased blood flow (redness, local heat) to infected/damaged area
_ ● activation of complement system, clotting system, fibrinolytic system, and kinin system
__leukocyte adhesion cascade
__ ● endothelial gaps increase vascular permeability and allow extravasation of serum proteins (exudate) and leukocytes (→ neutrophilsmacrophageslymphocytes) with resultant tissue swelling
___phagocytosis of foreign material with pus formation

The inflammatory response is part of the innate immune response, and employs cellular and plasma-derived agents (pathway):
complement system
interferons (IFN)
cytokines, lymphokines, monokines
prostaglandins and leukotrienes – arachidonic acid derivatives
● platelet activating factor (PAF)
● histamine
kinins (bradykininpain)

Pain-evoking mediators include proinflammatory cytokines, chemokines, protons, nerve growth factor, and prostaglandins, which are produced by invading leukocytes or by local cells.

Acute phase proteins fluctuate in response to tissue injury and infections. They are synthesized (by hepatocytes) in response to pro-inflammatory cytokines and include:
C-reactive protein (CRP),
mannose-binding protein,
complement factors,
alpha-1 acid glycoprotein,
alpha 1-antitrypsin,
alpha 1-antichymotrypsin,
alpha 2-macroglobulin,
serum amyloid P component (SAP, amyloid),
haptoglobins (alpha-2-globulins),
complement components C3, C4 ,
coagulation factors (fibrinogen, prothrombin, factor VIII, von Willebrand factor, plasminogen)● ferritin

Pro-inflammatory cytokines include IL-1, IL-6, IL-8, TNF-α (tumor necrosis factor alpha), and TNF-β (lymphotoxin α, LT).

In response to infection, macrophages secrete IL-1 and TNFs, which are broad-spectrum cytokines that stimulate inflammatory responses of neutrophils, fibroblasts, and endothelial cells. The fibroblasts and endothelial cells respond to IL-1 and TNF by recruiting more immune cells to the site of inflammation.

When tissue is destroyed or invaded by leukocytes in inflammation, numerous mediators are delivered by the circulation and/or liberated from resident and immigrated cells at the site. Proalgesic mediators include proinflammatory cytokines, chemokines, protons, nerve growth factor, and prostaglandins, which are produced by invading leukocytes or by resident cells. Less well known is that analgesic mediators, which counteract pain, are also produced in inflamed tissues. These include anti-inflammatory cytokines and opioid peptides. Interactions between leukocyte-derived opioid peptides and opioid receptors can lead to potent, clinically relevant inhibition of pain (analgesia). Opioid receptors are present on peripheral endings of sensory neurons. Opioid peptides are synthesized in circulating leukocytes, which migrate to inflamed tissues directed by chemokines and adhesion molecules. Under stressful conditions or in response to releasing agents (e.g., corticotropin-releasing factor, cytokines, noradrenaline), leukocytes can secrete opioids. They activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of excitatory neuropeptides. This review presents discoveries that led to the concepts of pain generation by mediators secreted from leukocytes and of analgesia by immune-derived opioids.
Leukocytes in the regulation of pain and analgesia. Rittner HL, Machelska H, Stein C. J Leukoc Biol. 2005 Dec;78(6):1215-22. Epub 2005 Oct 4. [Free Full Text Article]

[] inflammatory initiation - skin Џ animation of leukocyte adhesion Џ

Tables  Fc receptors  Immune Cytokines  Immunoglobulins  Cell Adhesion Molecules  Cell signaling  Receptor Tyrosine Kinases (RTKs)  Receptor Signal Transduction  Second Messengers 

▲ф agents : cytokines : events : pro-inflammatory cytokines : sequence : signs/symptoms ▲ф



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