inflammatory mediators

inflammatory mediators

1. be found in tissues in concentrations that can explain the observed symptoms or effects.

2. .. be released by the endogenous trigger which produces the response

3. .. have the same action in all species where the phenomenon occurs

4. .. be destroyed locally or systemically to avoid undue accumulation

5. .. be blocked (directly or indirectly) by inhibitors of inflammation.

6. Rocha E Silva, 1978

7. Plasma proteins such as complement and antibodies

   • complement
     • A complex series of about 20 proteolytic enzymes in the blood

8. Other proteins such as sPLA2 and acute phase reactants

9. Cytokines and chemokines

   • induce NOS

10. Lipids such as prostaglandins and PAF

    • prostaglandins discovered in 1930s
      • from fatty acids
      • in seminal vesicles
    • PAF
      • phospholipid
      • Causes increased vascular permeability, PMN migration, brochoconstriction and many other signs and symptoms of inflammation

11. Amines such as histamine

    • histamine
      • histamine molecule
      • peripheral algogen (keele 1969)
      • Stored in high concentrations in mast cells and basophils together with heparin and ATP.
      • Three main receptor subtypes (H1 etc).
      • Causes ‘triple response’.
      • early last century was synthesised and noted to have reaction like insect bites
        • but then realised other mediators when developed anti-histamines (1940s)
    • 5HT (monoamine)
      • 5HT
      • in platelets, neurones and in CNS. Often stored with other transmitters. Inactivated by MAO
      • does it release histamine in humans?

12. ‘Gasses’ such as NO and O2-

    • NO
      • different sorts of NOS
        • NOS/iNOS
      • vasodilator and microbicidal
      • induced in cells by cytokines, TNFa, IL1b or LPS
      • inhibition e.g. by IL10
    • O2

13. Kinins such as bradykinin

    • bradykinin

14. Neuropeptides

    • Tachykinins
      • substance P
        • act on 7tm receptors e.g. NK1
        • Cause vasodilatation, vascular permeability, smooth muscle contraction, mucus secretion, PAIN
      • neurokinin A&B
        • see SP
      • CGRP
        • CGRP
        • Induces neurogenic inflammation
    • Kinins
      • bradykinin
        • B1 and B2 receptors
        • Produce; vasodilation, smooth muscle contraction, PAIN and inflammation
      • kallidin
        • see bradykinin