This document discusses several biochemical mediators involved in inflammation including renin, angiotensins, kinins, prostaglandins, leukotrienes, cytokines, and platelet-activating factor (PAF). It describes where these mediators are synthesized, their receptors, actions on various organ systems, and physiological roles. Key points include that kinins are potent vasodilators, prostaglandins can cause fever by acting on the hypothalamus, leukotrienes recruit immune cells and cause bronchoconstriction, and cytokines coordinate the immune response and cellular functions.

1. Dr. Resu Neha Reddy
Post Graduate
Dept of Pharmacology
Osmania Medical College
Angiotensin, Kinins, Leukotrienes,
Prostaglandins & Cytokines

2. Renin
 Synthesised  Prorenin
 Prorenin and renin stored  Juxtaglomerular cells
of kidney
 3 mechanisms :
 Decrease renal perfusion  reduced tension in
vessel wall
 Decrease Na+ conc.  distal tubule
 Beta 1 adrenoceptors ++
 PGI2 ++
 Half-life – 15 min

3. ANGIOTENSINS
 Peptide harmones 
Angiotensinogen

4. ANGIOTENSINS

7. KININS
 Vasoactive polypeptide released from alpha 2 globulin
fraction of plasma  Kininogen  by the action of
specific enzymes Kallikreins
 Potent vasodilator peptides
 3 kinins  Bradykinin  nanopeptide
Kallidin  decapeptide
Met-Lys-bradykinin  undecapeptide

8. KININS
 Kininogens  2 types
 Low molecular weight kininogen (LMWK) 
Tissues
 High molecular weight kininogen (HMWK) 
Blood
 Kallikreins  2 forms
 Plasma Kallikrein
 Tissue Kallikrein

9. XII +

10. Synthesis & metabolism of
Bradykinin

12. KININ RECEPTORS
 2 types  B1 and B2
 Both are GPCR
B1 B2
Normally expressed at low levels but
are strongly induced in inflamed or
damaged tissues by cytokines such as
IL-1
Constitutively expressed in most
normal tissues
Respond to des-Arg9- bradykinin &
des-Arg9 kallidin but not to bradykinin
itself
Selectively binds bradykinin and
killidin and mediates the majority of
their effects
Likely that B1 receptors play a
significant role in inflammation and
hyperalgesia
B2 receptors activates PLA2 & PLC via
interaction with distinct G proteins

13. ACTIONS OF KININS
 CARDIOVASCULAR SYSTEM
 Kinins are more potent vasodilators than histamine
 Dilatation is mediated through endothelial NO & PGI2 generation
and involves mainly arterioles
 They markedly increase capillary permeability due to separation of
endothelial cell  exudation and inflammation
 Can release histamine and other mediators from mast cells
 Injected I.V kinins cause flushing, throbbing headache and fall in BP
 Kinins have no direct action on heart, reflex stimulation occur due
to fall in BP

14. ACTIONS OF KININS
 SMOOTH MUSCLES
 Kinin induced contraction is slow  Intestine, uterus & bronchi
 Cause marked bronchoconstriction in guineapig and in
asthmatic patients
 Fluid secretion in airways and GIT  cough & diarrhoea
 SENSORY NERVES
 Bradykinin stimulates pain nerve endings  Intradermally
 Elicit pain by stimulating nociceptive afferents in the skin and
viscera
 Produce  redness, local warmth, swelling and pain
 Important role in inflammation

15. Physiological role of Bradykinin
 Maintenance of BP
 Mediation of inflammation & pain
 Production of hyperaemia in various glands
 Tissue growth & repair
 Sperm motility

16. What are the features of
inflammation… ?
 Heat/fever
 Swelling
 Pain
 Redness
 Loss of function
 IN ONE WAY, fever and pain are beneficial ….. HOW ?

17. So both phenomenon are
beneficial

23. PGs produces FEVER....How?
 Hypothalamus contains thermoregulatory centre
 Maintains balance between heat production &
heat loss
 It regulates heat dissipating mechanisms

24. Increased
capillary
permeability
Infiltration
of
leucocytes
Vasodialation of
Some vascular
beds
Vasoconstriction
In
capillaries
Activation
of
kininogens
INFLAMMATION

25. BLOOD VESSELS
Vasoconstricto
r
Vasodilator

26. Reproductive Organs
Dysmenorrhoea
PDA

27. PGE2 + LTs
Contracts
Smooth muscle
PGE2: watery diarrhea,
Vomiting & cramps
(INC. cAMP)
PGE2 +PGI2: Inhibit gastric
acid secretion;
Cytoprotective effect
(INC.mucosal blood flow, cAMP,
mucous secretion, protein
synthesis)
GIT

28. PROSTAGLANDINS - USES
 Induction of abortion & cervical ripening
 Gastric cytoprotection  PGE1 (Misoprostol)
 Treatment of erectile dysfunction  Alprostadil injected
intracavernously
 Maintenance of patent ductus arteriosis  Alprostadil IV
 Primary pulmonary HTN  PGI2 ( Epoprostenol) IV
infusion
 Glaucoma  Latanoprost
 Peripheral vascular disease

29. Neutophils
MET: 20-hydroxy LTB4
Eosinophils, mast cells, basophils & macrophages
Metabolised & excreted : LTE4
Slow Reacting
Substance of
Anaphylaxis
(SRSA)

30. LEUKOTRIENE
Leukotriene receptors:
 BLT receptors : LTB4
 Cys-LT receptors : LTC4, LTD4 & LTE4
 All  GPCR  IP3/DAG transducer
mechanism

31. LEUKOTRIENE - Actions
BLOOD
LTB4 Potent chemoattractants
for neutrophils
(BLT1 receptor)
LTC4 & LTD4 (Cysteinyl LT) Potent chemoattractants
for eosinophils
 Eosinophil adhesion
 degranulation
 oxygen radical formation

32.  HEART & BLOOD VESSELS :
 LTC4 & LTD4  reduce myocardial contractility &
coronary blood flow (cardiac depression)
 Imp. Role in myointimal proliferation
 after vascular injuryangioplasty
• GIT :
• LTB4  neutrophil chemotaxis – IBD (colonic
mucosa)
LEUKOTRIENE - Actions

33.  BRONCHIAL SMOOTH MUSCLE:
 Bronchoconstriction
 Increased permiability
 Increased secretion
 LTC4, LTD4 & LTE4  ASTHMA
 INFLAMMATION:
 LTD4  imp. Mediator  all inflammations
 Eg: Rheumatoid arthritis
Psoriasis
Ulcerative colitis
LEUKOTRIENE - Actions

34. CYTOKINES
 Inflammation is an integral part  body defence
mechanisms
 Against foreign insults
 Natural & acquired immunity  human defence
 Mediated by protein hormones  CYTOKINES
 Released from variety of cells in response to no. of
stimuli

36. Classification of Cytokines
 Haemotopoietin family
Eg: GM-CSF, IL-2, IL-4
 Interferon family
Eg: Alpha, beta, gamma, IL-10
 Chemokine family
Eg: IL-8, monocyte chemotactic protein,
neutrophil activating protein, platelet factor 4
 Tumour necrosis factor (TNF)
Eg: TNF alpha, TNF beta, TNF gamma

38.  Defence role - alerting the body to invasion &
dealing with it
 Repair role - cleaning up the debris & replacing
lost matrix & tissue
 Controlling cellular proliferation &
differentiation
 Haematopoiesis
Functions of Cytokines

39. Secreted by Macrophages

40. From Th1 cells
Secreted by all T cells

42. From Th2 cells

43. Platelet – activating factor (PAF)
 Mediator in inflammation & allergies
 Misnomer  platelet stimulation ++  the name
Lyso-PAFLysoglyceryl-phosphoryl choline

44. Pharmacological actions of PAF
 Vasodilatation
 Increased vascular permeability
 Chemotactic – eosinophils & neutrophils
 Activation & aggregation of platelets ( TXA2)
 Activation of leucocytes
 Implicated in inflammation & bronchial hyper-
responsiveness
 PAF produced by foetus at final term  progression of
labour
 Most potent peptic ulcerogen

45. THANK YOU....