Inflammation

-Inflammatory stimulus is sensed by resident sentinel cells--> release of proinflammatory factors--> increased local blood flow and vascular permeability
-exudate (fluid/plasma) & cells from the blood move into the local tissue area
-neutrophils and monocytes/macrophages migrate via chemotaxis to area of inflammation

-PPRs found in resident immune cells (macrophages, dendritic cells, mast cells)
-PPRs recognise pathogens via PAMPs & DAMPs (Damage-associated molecular patterns) from damaged cells
-when stimulua is detected --> proinflammatory cytokines & other mediators are released

Toll like receptors (TLRs), C-type Lectins (CLRs), and Nod-like receptors (NLRs)

•Release cytokines and inflammatory mediators that trigger inflammatory responses, including recruitment more immune cells

Release mediators that cause vasodilation* e.g., prostaglandins and Nitric Oxide (NO)

-Heat (Calor) - vasodilation/increased blood flow and inflammatory mediators
-Redness (Rubor) - vasodilation/increased blood flow
-Swelling (Tumor) - exudate/increased fluid into tissues (oedema)
-Pain (Dolor) - physical and chemical stimulation of nociception
Loss of function - damage to cells, tissues

-(e.g., neutrophils & monocytes)
-Responsible for phagocytosis and cytokine release
Attracts other leukocytes to the area

Chronic inflammation

•Tumour necrosis factor (TNF)-α
•Interleukin-1 (IL-1) and IL-6

form of cytokine that control leucocyte migration e.g. LTB4

Flush (arterial vasodilatation)
Wheal (odema/swelling)
Flare (sensory nerve induced dilatation - CGRP)

-constricts bronchial SM
-Increases vascular permeability
-Evokes wheal and flare

Indication: Symptomatic relief of allergy such as hay fever, chronic idiopathic urticaria
MOA: Antagonist of Histamine H1 receptors

Non-selective inhibition of COX 1 and 2
Irreversible inhibition of COX-1 (antiplatelet)

Nonselective inhibitor of COX-1 and COX-2

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin

Non-selective inhibition of COX 1 and 2

•Mild: discomfort, dyspepsia and diarrhoea
•Severe: bleeding and ulceration

-Reduce PG synthesis
•Reduce cytokine generation
•Reduce production of NO
•Increase anti-inflammatory factors (IL-1, Il-10 annexin-1)
•Decreased action of leukocytes/immune cells
•Decreased fibroblast function

•Susceptibility to injury or infection
•Changes in electrolytes (hyperglycemia)
•Osteoporosis
•Mental health problems
•Cushing's syndrome --> weight gain

glucocorticoid steroid action includes
-inflammatory mediators, increased anti-inflammatory mediators and reduce action of inflammatory cells