Use of thiazolide compounds for the prevention and treatment of viral diseases, cancer and diseases caused by intracellular infections
The invention provides for the use of pharmaceutical compositions comprising a thiazolide in the stimulation of the immune system in a subject in need thereof, thereby preventing and/or treating viral diseases, cancer and diseases caused by intracellular protozoan infections.
1. A method of stimulating an immune response in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a thiazolide compound, wherein the thiazolide compound is nitazoxanide, tizoxanide, a mixture nitazoxanide and tizoxanide, N-(5-chlorothiazol-2-yl)-2-hydroxybenzamide, or a salt, ester, or amide thereof.
2. The method of claim 1 , wherein the thiazolide compound is nitazoxanide, tizoxanide or a mixture thereof.
3. The method of claim 1 , wherein the thiazolide compound is N-(5-chlorothiazol-2-yl)-2-hydroxybenzamide.
4. The method of claim 1 , wherein the thiazolide compound is administered in combination with a vaccine.
5. The method of claim 4 , wherein the vaccine is a tumor cell vaccine.
6. The method of claim 1 , wherein the thiazolide compound is administered in combination with an immunostimulant.
7. The method of claim 1 , wherein the thiazolide compound is administered in combination with an anticancer drug.
8. The method of claim 7 , wherein the anticancer drug is selected from the group consisting of STI571, CGP 74588, 1-β-D-Arabinofuranosylcytosine (Ara-C), doxorbicin, dacarbazine, cisplatin, bleomycin, vincristine, lomustine, vinblastine, carmustine, DTIC, tamoxifen, sunitinib, sorafenib and interferon-α.
9. The method of claim 1 , wherein said administering stimulates T helper cell or CTL activity, TLR7 or TLR8 expression or type I interferon response in the subject.
10. The method of claim 9 , wherein said administering induces an increase in at least one of 1) IFNγ- and IL2-secreting CD4+ T cells, 2) CTL degranulation, 3) Fas-expressing CD8+ T cells, 4) TLR8-expressing monocytes, 5) IFNα and IFNβ-mRNA expression, 6) mRNA specific for a type 1 IFN inducible gene and 7) mRNA specific for a gene involved in MEW class presentation.
11. The method of claim 10 , wherein the type 1 inducible gene is at least one of MXA, PRKCZ, ADAR, CXCL10, IFR1 and PRKRA.
12. The method of claim 10 , wherein the gene involved in MEW class I presentation is at least one of HLA-A, HLA-B and TAP1.
13. The method of claim 10 , wherein said administering induces an increase in 1) IFNγ- and IL2-secreting CD4+ T cells, 2) CTL degranulation, 3) Fas-expressing CD8+ T cells, 4) TLR8-expressing monocytes, 5) IFNα and IFNβ-mRNA expression, 6) mRNA specific for a type 1 IFN inducible gene and 7) mRNA specific for a gene involved in MHC class presentation.
14. The method of claim 2 , wherein the thiazolide compound is administered orally.