HOST MODULATION

 

'Host' - The organism from which a parasite obtains nourishment.

'Modulation' - Alteration of function or status of something in response to a stimulus or an altered chemical/ physical environment.

Host Modulation Therapy (HMT) is a treatment concept that helps restore the balance of pro-inflammatory, anti-inflammatory mediators to that seen in healthy individuals by modifying host response factors.

Plaque bacteria initiates the disease and bacterial antigens cross the junction epithelium and drive the inflammatory process. Bacteria are essential for periodontitis to occur but a susceptible host is even more important.

Page et al., in 1997, reported that PDL breakdown is caused by host destructive enzymes like metalloproteinases (MMP'S), prostaglandins (PG), interleukins (IL).

HMT AGENTS-

1. Sub-antimicrobial dose doxycycline- According to Burns et al., in 1989, doxycycline was most potent tetracycline in inhibition of collagenolytic activities. Sub dose was shown to be efficient in inhibiting mammalian collagenase activity without developing resistance.

2. NSAIDS- They inhibit the formation of prostaglandins. PGI2 increases in periodontal diseases and also has an inhibitory effect on fibroblast function and immune response. They are used to treat pain, inflammation and other chronic inflammatory conditions.

3. COX-2 inhibitors- COX-2 is induced after stimulation by cytokines, growth factors and lipopolysaccharides which increase prostaglandins. Inhibition of COX-2 was of great help in reducing periodontal inflammation and it even slowed down alveolar bone loss.

4. Bisphosphonates- They are bone seeking agents that inhibit bone resorption by disrupting osteoclastic activity. They interfere with osteoblast metabolism and secretion of cytosomal enzymes. They also possess anti collagenase activity.

New Agents-

• NO synthase inhibitors
• Recombinant human IL-11
• Omega-3 fatty acid
• Mouse anti-human IL-6 receptor antibody

Disruption of RANK/RANKL

The RANK/RANKL interaction is responsible for differentiation and maturation of osteoclast precursor cells to activate osteoclasts.

Osteoprotegerin acts as a decoy receptor, expressed by osteoblastic cells, which binds to RANKL and inhibit osteoclast development.

Disruption of Cell Signalling Pathway

Inhibition of signal transduction pathways would be expected to abolish both cell activation by cytokines or other stimuli and production of proinflammatory cytokines.

Signal transduction pathways involved in inflammation include- 

• Mitogen activated protein kinase pathway
• JAK-STAT pathway
• P13 pathway

Receptors involved in pathways-

• G-protein coupled receptors
• Chemokine receptors
• Integrins
• Selectins 

5. MAPK inhibitors- Inhibit LP's induced MMP, cytokines ( IL-1b, TNF-alpha, IL-6, IL-8 )

     NF-kB family inhibitors- Inhibit NF-kB dependent expressions ( IL-6,8,1, MMP's, IFN-c )