Lecture 1: Intro Inflammation Flashcards
Inhibits cytokines
Etanercept and Infliximab
Inhibits prostaglandins
Aspirin and NSAID
Inhibits leukotrienes
Zileuton and Zafirlukast
What inhibits cytokines, prostaglandins, leukotrienes, cell adhesion molecules
Steroids
What are the cardinal signs of actue inflammation
Red, heat, pain, swelling, LOF
Physiological responses to ACUTE inflammation
Vasodilation, Increase in vascular permeability, accumulation of inflammatory cells (neutrophils)
What is the main cell type associated with chronic and main characteristic
Macrophage (Monocyte), Fibrosis
What is the main cell type associated with acute inflammation and its main characteristic
Neutrophils, and edema
Histamine
A biogenic amine.
Stored in mast cells and basophils (non-mast cell sources in neurons and cells in the stomach).
Response is: vasodilation, increased vascular permeability, and pain.
Mechanism: Activation of GPCRs.
Pharmacology: antihistimines (H1 antagonists)
Bradykinin
A peptide.
From endothelial cells.
Response: Vasodilation, increased microvessel permeability, pain.
Mechanism: Activation of GPCRs.
Pharmacology: BK receptor antagonists being tested
Complement System
Plasma proteins.
Source by synthesis by liver circulating in blood.
Response: Chemotaxis, promote relase of mediators from neutrophil, increase vascular permeability, excessive activation may contribute to tissue injury.
Mechanism: Complement protein complex causes osmotic lysis, activation of GPCRs.
C-Reactive Protein
A plasma protein.
Source by prodused in liver in response to cytokines, also produced in adipocytes.
Response: Acute-phase reactant, activates complement cascade, mediates phagocytosis, marker of inflammation.
Mechanism: Binds to phosphotidylcholine-containing substances in bacteria and damaged cells, calcium dependent binding.
Pharmacology: Too much CRP assoc with increased risk of diabetes, hypertension, and CV disease. No CRP inhibitors developed, Statins may be effective in reducing CRP levels
What is acute phase reaction
In response to injury, local inflammatory cells secrete cytokines that cause the liver to increase or decrease production of various proteins. An acute phase protein is one whose plasma concentration changes from baseline by at least 25% during inflammation.
What are the important cytokines
TNF-alpha, Interleukin-1 (IL-alpha, IL-beta)
Cytokines
A secreted protein.
Source by nearly all cells.
Response: Stimulate acute phase reactants.
TNF-alpha: fever, sepsis
IL-1: fibroblast and lymphocyte proliferation, fever
Mechanism: Interaction with specific receptors to induce gene expression of number of proteins through activation of transcription factors, such as NF-kB and AP-1.
Pharmacology: Etanercept, inflixamab
What are the results of activation of NFkB and AP-1
Increase cyclooxygenase (fever) and lipooxygenases. Increase adhesion molecule expression. Induce collagenase (fibrosis
TNF-alpha
Stimulates acute phase reaction, fever, sepsis
IL-1
Stimulates acute phase reaction, fibroblast and lymphocyte proliferation, fever
Adenosine
A purine nucleoside formed from ATP breakdown.
Source: all cells.
Response: Increases extracellularly during injury and has an anti-inflammatory effect to inhibit cytokine action, receptor specific.
Mechanism: via specific GPCRs.
Pharmacology: A2 agonists, methotrexate (releases adenosine), Adenosine A3 antagonists in asthm/inhibit mediator release.
Cell adhesion molecules
A family of proteins.
Source: endothelial cells, platelets, leukocytes.
Response: Leukocyte adhesion to endothelium, endothelial adhesion molecules contribute to recruitment of activated platelets.
Mechanism: contact molecules, calcium dependent.
Oxygen-derived free radicals
Superoxide, hydroxy radicals. Source: all cells. Response: intracellular killing of bacteria by neutrophils. Mechanism: protein oxidation, lipid peroxidation, DNA mutations. Pharmacology: anti-oxidants like Vit C and E
What are the lipid mediators
Prostaglandins. Leukotrienes. Steroids
Prostaglandins
Source: almost all cells. Response: Vasodilation/vasoconstriction, pain, fever, platelet aggregation (via thromboxane). Mechanism: Activation of specific GPCRs. Pharmacology: NSAIDS
Leukotrienes
Source: Macrophages and Neutrophils. Response: Increased vascular permeability, and Bronchoconstriction. Mechanism: GPCRs. Drugs: 5-lipoxygenase inhibitors (Zileuton), leukotriene receptor antagonist (Zafirlukast)
