Chemical mediators of inflammation – B. Pharma 2nd Semester Pathophysiology notes pdf

Chemical mediators of inflammation

Chemical mediators of inflammation

Objective

At the end of this lecture, student will be able to

         List various chemical mediators of inflammation

         Describe the formation and functions of cell derived mediators

        Describe the formation and functions of plasma derived mediators

Chemical mediators of inflammation

       Endogenous compounds

       Released during inflammation

       Increases vascular permeability

       Edema, Destruction of inflammatory agents

Chemical mediators of inflammation

Cell-derived mediators of inflammation

       Vasoactive amines – Histamine, Serotonin, Neuropeptides

       Arachidonic acid metabolites

      Via COX pathway – Prostaglandins, Thromboxane A2, prostacyclin

      Via LOX pathway – 5-HETE, leukotrienes

       Lysosomal system

       Platelet activating factor

       Nitric oxide and oxygen metabolites

Plasma derived mediators of inflammation

       The kinin system

       The clotting system

       The fibrinolytic system

       The complement system

Vasoactive amines (Autocoids)

Amine autocoids

       Histamine

       5 – HT / Serotonin

Released within 1 hour of inflammatory response

 Histamine

       Stored in mast cells, basophills & platelets

Released due to – Heat/cold radiations

          –      Chemical irritant & immunological reactions

          –      Anaphyla toxins

Main actions of Histamine

       Vaso dilation

       ↑ permeability of venules

       Itching & pain

       Release of other cell derived mediators

       Broncho constriction

Serotonin

       Present in chromaffin cells of GIT

       In spleen, nervous system, mast cells & platelets

Actions

       Vasodilation

       ↑vascular permeability

       Less potent than histamine

Neuropeptides

       Tachykinin neuropeptides – substance P, neurokinin A, vasoactive intestinal polypeptide (VIP) & somatostatin

       Produced in the central and peripheral nervous systems

Actions

       Increased vascular permeability

       Transmission of pain stimuli

       Mast cell degranulation

Arachdonic acid Metabolite

       Tissue injury – Phospholipase A2 activation

       Conversion of phospholipids into arachdonic acid

Metabolism of arachdonic acid follows 2 pathway

       COX (Cyclo-oxygenase) – Pathway

       LOX (Lipo- oxygenase) – Pathway

COX Pathway

COX Pathway

LOX Pathway

LOX Pathway

Lysosomal components

Granules of Neutrophills

Primary granules 

·
Myeloperoxidase

·       Acid hydrolase

·       Neutral proteases

Secondary granules

·       Lactoferrin

·       Lysozyme

·       Alkaline phosphatase

·       Collagenase

Granules of Monocytes & Tissue macrophages

       Cells on degranulation releases mediators like

       Acid proteases

       Collagenase

       Elastase

       Plasminogen activator

More involved in chronic inflammation

Platelet Activating Factor (PAF)

IgE-sensitised basophils or mast cells, other leucocytes, endothelium and platelets

     ↑ vascular permeability

     Vasodilatation in low concentration and vasoconstriction

     Broncho constriction

     Adhesion of leucocytes to endothelium

     Chemotaxis

Cytokines

     Group of polypeptide substances

     Produced by activated lymphocytes/ monocytes

     Interleukin 1 & 8

     Tumor necrosis factor

     Interferon

     Platelet factor

Actions:

     IL –I, TNF α & β – ↑ leucocyte adherence, Platelet aggregation, proliferation of fibroblast

     Interferon gamma – activation of macrophages & neutrophils

     IL-8 – Chemotactic of neutrophills

     PF – 4 – Chemotactic for neutrophills, monocytes & eosinophills

Nitric oxide & oxygen metabolites

     Released by activated macrophages from vascular endothelium

     Vasodilation

     Inhibiton of platelet aggregation

     Killing of micro organism

     O2 free radicals released from activated neutrophills & macrophages

     Endothelial damage

     ↑vascular permeability

     Tissue matrix damage

Plasma derived mediators

     Interlinked system

     Include

    Clotting system

    Kinin system

    Fibrinolytic system

    Complement system

     Hageman factor (Factor XII) – connects the other 4 system

Plasma derived mediators

Clotting system

     Results in formation of fibrinogen

     Thrombin converts fibrinogen to fibrin & fibrinopeptide

    ↑ vascular permeability

    Chemotaxis of leucocytes

    Anticoagulant activity

Fibrinolytic system

     Activated by plasminogen

     Plasminogen activator – plasminogen – plasmin-  breakdown of fibrin –  fibrinopeptides or fibrin split products

Actions

    Activation of factor XII

    Splits complement fraction C3to C3a– permeability factor

    Degrade fibrin to form fibrin split products

Complement system

Involves 2 pathways

     Classic pathway through antigen-antibody complexes

     Alternate pathway via non-immunologic agents such as bacterial toxins, cobra venoms and IgA

Anaphylatoxins (C3a, C5a, C4a)

    Activate mast cells and basophils to release of histamine

    cause increased vascular permeability

    augments phagocytosis

     C3b – an opsonin

     C5a –  chemotactic for leucocytes

     Membrane attack complex (MAC) (C5b-C9) is a lipid dissolving agent and causes holes in the phospholipid membrane

Chemical mediators of inflammation

Chemical mediators of inflammation

Summary

     Chemical mediators are endogenous compounds released during inflammation which increases vascular permeability, bring about edema and destruction of inflammatory agents

     Chemical mediators of inflammation are derived from cell and plasma

     Cell-derived mediators include histamine, serotonin, leukotrienes, platelet activating factors, cytokinines, prostaglandins

     Plasma derived mediators include kinin system, cltting and fibrinolytic system and clotting system

Frequently asked questions (FAQs)

1. What are chemical mediators of inflammation?

Chemical mediators of inflammation are signaling molecules produced by the body in response to injury or infection. They play a crucial role in initiating, amplifying, and resolving the inflammatory response.

2. What is the primary purpose of these chemical mediators?

The primary purpose of chemical mediators of inflammation is to coordinate the immune response, including the recruitment of immune cells, regulation of blood flow, and the resolution of inflammation after the threat is neutralized.

3. What are some common proinflammatory mediators?

Common proinflammatory mediators include histamines, prostaglandins, leukotrienes, cytokines (such as interleukins and TNF), and chemokines.

4. How do anti-inflammatory mediators work to resolve inflammation?

Anti-inflammatory mediators, like lipoxins, resolvins, and TGF-β, work by promoting the resolution of inflammation. They help reduce inflammation, prevent excessive immune cell recruitment, and aid in tissue repair.

5. Can inflammation be harmful in some cases?

Yes, while inflammation is a vital defense mechanism, chronic or excessive inflammation can lead to various diseases, including autoimmune conditions and chronic inflammatory disorders.

6. What is the role of prostaglandins in inflammation?

Prostaglandins are lipid compounds that play a crucial role in inflammation. They are involved in vasodilation, pain, fever, and regulating the immune response.

7. How do cytokines contribute to the inflammatory response?

Cytokines are signaling proteins that coordinate immune cell activities during inflammation. They can either promote or inhibit inflammation, depending on their type and role.

8. Are there natural ways to modulate inflammation using diet and lifestyle?

Yes, maintaining a healthy diet rich in anti-inflammatory foods (e.g., fruits, vegetables, and omega-3 fatty acids) and adopting a lifestyle that includes regular exercise can help manage and reduce inflammation.

9. Can understanding chemical mediators lead to better treatments for inflammatory conditions?

Yes, understanding the roles of chemical mediators in inflammation is crucial for developing targeted treatments for various inflammatory conditions. Researchers continue to explore these pathways to develop more effective therapies.

10. What happens when the balance between proinflammatory and anti-inflammatory mediators is disrupted?

When this balance is disrupted, it can lead to chronic inflammation or a weakened immune response, both of which can have adverse effects on health.

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