MEDIATORS OF INFLAMMATION

• 1. HISTAMINE
RELEASED FROM MAST CELLS
VASODIALATOR ( HYPEREMIA )
BRONCHOCONSTRICTOR
TYPE 1 ALLERGY
• EARLY RESPONSE AND DELAYED RESPONSE OF
HISTAMINE

• EARLY DUE TO DEGRANULATION

• DELAYED DUE TO LEUCOTRINES

• 2. SEROTONIN
• ACTIONS SIMILAR TO HISTAMINE
• VD
• BC
 5HT OR SEROTONIN
• CARCINOID SYNDROME
• VD SO REDNESS OR FLUSHING OF SKIN OR DIALATATION OF GI TRACT
HENCE DIARRHOEA
• BC SO COUGH AND SOMETIMES COUGH WITH SPUTUM AND EVEN IN
BLOOD
• MOST COMMON SITE OF CARCINOID TUMOR
• GIT ( ILLEUM ) THEN APPENDIX
• SOME MAY HAVE CARCINOID IN LUNGS ( BRONCHUS ) BRONCHIAL
CARCINOID WITH MASSIVE HAEMOPTYSIS.
• IN HEART IT AFFECTS RIGHT SIDE OF HEART HENCE TRICUSPID VALVE
BECAUSE IN LEFT SIDE WE HAVE MAO WHICH DEGRADE THIS SEROTONIN.

• DIAGNOSED BY
• MEASURING 5HIAA HYDROXY INDOLE ACETIC ACID IN URINE .
• AND CHROMOGRANIN IN BLOOD
 3. ARACHADONIC ACID METABOLITE
• PHOSPHOLIPID INTO AA BY PHOSPHOLIPASE
• AA FURTHER ACTED BY TWO PATHWAYS
• COX ( COX1 <PHYSIOLOGICAL OR CONSTITUTIVE ENZYME> COX2
<PATHOLOGICAL OR INDUCIBLE ENZYME > COX3 < PCM ACTS ON
COX 3 > ) AND LOX PATHWAY
• COX PRODUCTS ARE PG ( PGD2 PGE2 ND PGF2 ALPHA) ,
PROSTACYCLINS AND THROMBOXANE A2 ( AGGREAGATION OF
PLATELETS ).
• LOX PRODUCTS ARE LT < LTA4 , LTB4 ( IN CHEMOTAXIS ) , LTC4 LTD4
LTE4 ( THESE C4 D4 E4 ARE CALLED SRSA IE SLOW REACTING
SUBSTANCES OF ANAPHYLAXIS )> AND LIPOXINS ( ALSO HAVE ANTI
INFLAMMATORY ACTIVITY ) .
• STEROIDS INHIBIT PHOSPHOLIPASE ENZYME THUS NO AA FROMED
THUS INHIBITS COX AS WELL AS LOX PATHWAY.
 4. COMPLEMENT SYSTEM
• C3 CONVERTASE GIVES C3a AND C3b
• C3b GIVES C5 CONVERTASE
• C5 CONVERTASE GIVES C5A C5B
• C5B – 9 CALLED AS MAC ( MEMBRANE
ATTACKING COMPLEX ) CAUSE LYSIS OF CELL.
• C3A AND C5A ARE CALLED ANAPHYLOTOXINS
• C3B IN OPSONISATION
• C5B-9 CALLED MAC
DEFECTS IN COMPLEMENT SYSTEM
• 1. C5B- 9 DEFICIENCY ( MAC DEFICIENCY )
• RISK OF NEISSERIAL INFECTIONS
• 2. C1 INHIBITOR DEFICIENCY
• RISK OF HEREDITARY ANGIOEDEMA
• OEDEMA NEAR ORBIT OF EYES
 5. NO
• SYNTHESISED FROM N- AA L-ARGININE
• POTENT VASODIALATOR AT 2 PLACES
• PULMONARY CIRCULATION AND GENITALS
• GET METABOLISED BY ENZYME 5
PHOSPHODIESTERASE
• NTG AND NTP AND 5PDE INHIBITOR ( SIDENAFIL )
ALL THESE TOGETHER THEN EXCESSIVE
VASODIALATION OF PULMONARY CIRCULATION (
LOW BP, SHOCK AN DEATH ) AND GENITALS.
 6. TOLL LIKE RECEPTORS
• ACTIVATED BY PAMP PATHOGEN ASSOCIATED
MOLECULAR PROTEIN
• ACTIVATE NFKB THEN MULTIPLE RESPONSE OF
INFLAMMATION.
 CYTOKINES
• IL-1/TNF : FEVER
• IL-6
• RELEASE NEUTROPHILS FROM MARROW
CHEMICAL MEDIATORS ENUMERATE
Cytokines