. 2020 Feb 13;6(3):191–198. doi: 10.1016/j.ijwd.2020.01.009

Table 1.

Mechanism of action of sulfasalazine.

Action of sulfasalazine	Mechanism
Immunomodulatory/anti-inflammatory action	Inhibition of cytokine release • T-cell cytokine IL-2 • Monocyte-macrophage cytokines IL-1, IL-6, IL-12, TNF Inhibition of 5-lipoxygenase pathway • ↓ leukotriene production Inhibition of nuclear factor-κβ transcription • ↓ expression of adhesion molecules (VCAM, ICAM, ELAM) Inhibition of chemotaxis and random migration of inflammatory cells such as neutrophils↓ superoxide and proteolytic enzyme productionInhibition of 5-aminoimidazile-4-carboxamide ribonucleoside transformylase enzyme • ↑adenosine at sites of inflammation ↑free radical scavenging activityOther in vitro anti-inflammatory effects: • Inhibition of prostaglandin E2 synthetase • Apoptosis of neutrophils • Inhibition of the extracellular release of pro-inflammatory secretory phospholipase A2 • B-cell suppression and immunoglobulin production
Antiproliferative action	Competitive inhibitor of brush border folate conjugase enzyme • Inhibition of polyglutamyl folate hydrolysis • ↓absorption of both polyglutamyl and monoglutamyl folate
Antibacterial activity	Competitive inhibition of the bacterial enzyme dihydropteroate synthetase, necessary for the synthesis of folic acid

Action of sulfasalazine

Mechanism

Immunomodulatory/anti-inflammatory action

Inhibition of cytokine release

•
T-cell cytokine IL-2
•
Monocyte-macrophage cytokines IL-1, IL-6, IL-12, TNF

Inhibition of 5-lipoxygenase pathway

•
↓ leukotriene production

Inhibition of nuclear factor-κβ transcription

•
↓ expression of adhesion molecules (VCAM, ICAM, ELAM)

Inhibition of chemotaxis and random migration of inflammatory cells such as neutrophils↓ superoxide and proteolytic enzyme productionInhibition of 5-aminoimidazile-4-carboxamide ribonucleoside transformylase enzyme

•
↑adenosine at sites of inflammation

↑free radical scavenging activityOther in vitro anti-inflammatory effects:

•
Inhibition of prostaglandin E2 synthetase
•
Apoptosis of neutrophils
•
Inhibition of the extracellular release of pro-inflammatory secretory phospholipase A2
•
B-cell suppression and immunoglobulin production

Antiproliferative action

Competitive inhibitor of brush border folate conjugase enzyme

•
Inhibition of polyglutamyl folate hydrolysis
•
↓absorption of both polyglutamyl and monoglutamyl folate

Antibacterial activity

Competitive inhibition of the bacterial enzyme dihydropteroate synthetase, necessary for the synthesis of folic acid

ELAM, endothelial cell adhesion molecule; ICAM, intercellular adhesion molecule; IL, interleukin; TNF, tumor necrosis factor; VCAM, vascular cell adhesion molecule.