COMMONLY USED IMMUNOMODULATOR

1. Immunomodulators

2. Introduction
• Potentially hostile world - array
of infectious agents
• Proverbial double edged sword.

3. Definition
Helps in regulation of the immune system

4. Indications
 Treatment of autoimmune diseases
 Recurrent diseases
 In case of organ transplant.
 Immunodeficiency disorders(AIDS)
 Chronic infectious diseases.
 Cancer particularly disorder involving the lymphatic
system

5. Classification of Immunomodulators
Immunosuppressants
Immunostimulants

6. Immunosuppressive Drugs
Drugs that are used to inhibit / prevent activity of immune
system
1. Glucocorticoids
2. Cytostatics
3. Antibodies
4. Drugs acting on immunophilins
5. Other drugs

7. 1. Glucocorticoids
Supress various allergic, inflammatory & autoimmune diseases
Mechanism of action:
Immunosuppressive action
 Suppress cell mediated immunity
 Suppress the humoral immunity
Antinflammatory action

8. Corticosteroids in oral diseases
 Topical
 Intralesional
 Systemic

9. Topical corticosteroids
Steroid Dosage every 6 hrs
Hydrocorticosone
hemisuccinate pellets
2.5 mg dissolve in
mouth close to ulcers
Triamcinolone
acetonide in carmellose
gelatin paste
Apply to lesion
More potent
Betamethasone
phosphate tablets
0.5 mg use as
mouthwash

10. Topical corticosteroids
Beclomethasone spray 1 puff 100 g
Budesonide spray 1 puff 100 g
Flucinolone spray Apply to lesion
Flucinonide cream gel or
ointment
Apply to lesion
Highly potent
Clobetasol cream Apply to lesion 5mg

11. Intralesional corticosteroids
Prednisolone sodium phospahte Up to 22 mg
Methylprednisolone acetate 4-80mg
Triamcinolone acetonide 2-3 mg
Triamcinolone hexaacetonide Up to 5mg

12. Systemic corticosteroids
Drug Dose
Prednisolone
40-80 mg orally daily in
divided doses
taper to 10 mg

13. Cytostatics
 Cytostatics inhibit cell divison –
T & B cell

14. Alkylating agents
Nitrogen mustards (Cyclophoshamide)
Mechanism of action:
1. Elimination of T regulatory cells(CD4+ CD25+)
2. Induction of T cell growth factors - Type I IFNs

15. Antimetabolites
Antimetabolites interfere with the synthesis of nucleic
acids
Methotrexate:
Inhibit metabolism of FA
Prevent synthesis of THF
Inhibition of T- cell activation

16. Azathioprine
Both cell- mediated & humoral immunity

17. Antibodies
Antibodies are used as a quick and potent
Immunosuppression
2 types:
1.Polyclonal antibodies
2 .Monoclonal antibodies

18. Antibodies
Polyclonal antibodies
Inhibit T lymphocytes & their lysis ,
Followed by removal of reticuloendothelial
cells from the circulation
Monoclonal antibodies
directed towards defined antigens

19. Drugs acting on Immunophilins
Cyclosporin
Bind M cytosolic protein -cyclophilin
Complex -inhibits calcineurin, which induces
transcription IL-2

20. Tacrolimus
Inhibits maturation, activation
Binds cytosolic proteins (Macrophilins I)
blocks calcineurin
Inhibits activated T cells, IL-2, 4, 5
IL-8 Receptors

21. Sirolimus
Sirolimus acts synergistically - cyclosporine
Inhibits T lympohocyte kinases & phosphatases
Prevent - G1 to S phase
B cell differentiation to plasma cells
Decreases IgM, IgG, IgA

22. Other drugs
Interferons
 IFN-β suppresses Th1 cytokines
 Monocyte activation

23. Thalidomide
 Immunomodulatory
 Anti-inflammatory
 Anti-angiogenic
 Modulates CD4+ and CD8+

24. Immunostimulators
DEFINITION:
Stimulate IMMUNE SYSTEM by
inducing activation/increasing
activity of any of its components

25. 2 categories (Immunostimulators)
A. Specific Immunostimulators
 Provide antigenic specificity in Immune Response
E.g. vaccines
B. Non specific Immunostimulators
 Act irrespective of antigenic specificity to
augment Immune Response E. g. adjuvant

26. Levamisole
 Restore depressed immune function
 Stimulate formation of antibodies to various
antigens
 Enhance T-cell responses
 Potentiate monocyte and macrophage
 Normalize CD4+ cell/CD8+ cell ratio

27. Indications In Oral Diseases

28. Indications In Oral Diseases
Corticosteroids
 RAS
 Bullous pemphigoid
 Mucous membrane pemphigoid
 Linear Ig A disease
 Oral Lichen Planus

29. Indications In Oral Diseases
Cyclophoshamide
Dosage:1-2.5 mg/kg/day
 Pemphigus Vulgaris
 Mucous Membrane Pemphigoid

30. Indications In Oral Diseases
Methotrexate
5-12.5 mg/week
 Oral Erosive Lichen Planus
 Pemphigus -100mg/day
 Bullous pemphigoid

31. Indications In Oral Diseases
Azathioprine
Dosage : 0.5-2.5 mg/kg/daily
 Pemphigoid
 Pemphigus
 Major Apthous Stomatitis
 Adjunct to prednisone
 Severe Erosive Lichen Planus
 Erythema Multiforme

32. Indications In Oral Diseases
Cyclosporin:
 Pemphigus - 5 -8mg/kg/day
 Bullous Pemphigoid
 Lichen Planus
 Behcets synd (1-2mg/kg/day)

33. Indications In Oral Diseases
Tacrolimus
0. 03%-0. 1% ointment
 Lichen Planus
 GVHD
 Cutaneous Lupus Erythematosus

34. Indications In Oral Diseases
Interferons
 Leukoplakia: IFN 6 MU/day3 times,4 wks
 OSMF: intra lesional injection of 50mg/0.25ml
twice a wk, for 8 wk

35. Indications In Oral Diseases
Thalidomide
100 - 300 mg/day
 Persistent / continuous Erthema Multiforme
 Severe RAS

36. Indications In Oral Diseases
Levamisole
50 mg t.i.d, 3days
,
 RAS
 Herpes Simplex Virus

37. Vaccines
Prophylactic
Caries vaccine
 To prevent, protect - tooth decay.
Therapeutic
 Autoimmune diseases
 Cancer

38. Adverse effects of immunomodulators
Glucocorticoids
 Osteoporosis
 Predisposition to infection
 Peptic ulcer
 Hyperglycemia
 Hypertension
 Edema
 Euphoria & psychosis

39. Adverse effects of immunomodulators
Cytostatics
 Anemia
 Neutropenia
 Dermatitis
 Non Hodgkin’s Lymphoma
 Squamous cell carcinoma

40. Drugs acting on Immunophilins
 Decreases kidney function
 Increases infection risk
 Mild tremor
 Swollen gums
 Peripheral tingling
 Hypertrichosis

41. Other drugs
 Influenza like illness
 Bone marrow suppression
 Hepatitis

42. Immunostimulator
 Nausea, vomiting,diarrhea
 Alopecia
 Neutropenia

43. Special considerations
 Patients should be free from other aliments
 Blood tests should be performed frequently
 Contraindicated in pregnancy

44. CONCLUSION
Wealth of knowledge about concepts of modern
immunology has led to development of specifically
targeted treatment
Central to 21st century medicine, steroid sparing drugs
Classed as investigational drugs, requires the
clinician to weigh the benefits against risks