TREATMENT OF MACROPHAGE-RELATED DISORDERS

1 . A method of reducing the side effects of an immunomodulator administered to a subject in need thereof, said method comprising administering an oxidative agent to said subject in combination with said immunomodulator.

2 . The method of claim 1 , wherein said immunomodulator is administered for the treatment of a macrophage-related disorder selected from the group consisting of cancer, multiple sclerosis, rheumatoid arthritis, macrophage activation syndrome, atherosclerosis, Type I diabetes, Type II diabetes, Kawasaki disease, asthma, hemophagocytic lymphohistiocytosis, sarcoidosis, periodontitis, Whipple's disease, pulmonary alveolar proteinosis, macrophage-related pulmonary disease, Leishmaniasis, hemodialysis-related inflammation, microbial infection, transplant-related complications, metabolic syndrome, hypertension, and inflammatory neurological diseases.

3 . The method of claim 1 , wherein said immunomodulator is selected from the group consisting of immunosuppressants, macrophage migration inhibitors, anti-inflammatory agents, and immunomodulatory antibodies.

4 . The method of claim 1 , wherein said oxidative agent is selected from

i) non-halogen activated-oxygen compounds selected from potassium nitrate (KNO 3 ), permanganate salts, ammonium cerium(IV) nitrate, hexavalent chromium compounds, chromate/dichromate compounds, ammonium silver nitrate, sulfoxides, persulfuric acid, osmium tetroxide (OsO 4 ), nitric acid, nitrous oxide (N 2 O), hydrogen peroxide, organic peroxides, superoxides, and ozone;

ii) non-oxygen activated-halogen compounds selected from fluorine, chlorine, bromine, and iodine;

iii) activated-halogen activated-oxygen compounds selected from sodium chlorite and tetrachlorodecaoxygen; and

iv) N-halo compounds selected from the group consisting of N-halophthalimide, N-halosuccinimide, N-halosaccharin, N,N-dihalourethane, N-haloacetanilide, 1,3-dihalo-5,5-dimethylhydantoin, trihaloisocyanuric acid, and sodium dihaloisocyanurate.

5 . The method of claim 1 , wherein said oxidative agent is sodium chlorite.

6 . A method of potentiating the effect of an immunomodulator administered to a subject in need thereof, said method comprising administering an oxidative agent to said subject in combination with said immunomodulator.

7 . The method of claim 6 , wherein said immunomodulator is administered for the treatment of a macrophage-related disorder selected from the group consisting of cancer, multiple sclerosis, rheumatoid arthritis, macrophage activation syndrome, atherosclerosis, Type I diabetes, Type II diabetes, Kawasaki disease, asthma, hemophagocytic lymphohistiocytosis, sarcoidosis, periodontitis, Whipple's disease, pulmonary alveolar proteinosis, macrophage-related pulmonary disease, Leishmaniasis, hemodialysis-related inflammation, microbial infection, transplant-related complications, metabolic syndrome, hypertension, and inflammatory neurological diseases.

8 . The method of claim 6 , wherein said immunomodulator is selected from the group consisting of immunosuppressants, macrophage migration inhibitors, anti-inflammatory agents, and immunomodulatory antibodies.

9 . The method of claim 6 , wherein said oxidative agent is selected from

i) non-halogen activated-oxygen compounds selected from potassium nitrate (KNO 3 ), permanganate salts, ammonium cerium(IV) nitrate, hexavalent chromium compounds, chromate/dichromate compounds, ammonium silver nitrate, sulfoxides, persulfuric acid, osmium tetroxide (OsO 4 ), nitric acid, nitrous oxide (N 2 O), hydrogen peroxide, organic peroxides, superoxides, and ozone;

ii) non-oxygen activated-halogen compounds selected from fluorine, chlorine, bromine, and iodine;

iii) activated-halogen activated-oxygen compounds selected from sodium chlorite and tetrachlorodecaoxygen; and

iv) N-halo compounds selected from the group consisting of N-halophthalimide, N-halosuccinimide, N-halosaccharin, N,N-dihalourethane, N-haloacetanilide, 1,3-dihalo-5,5-dimethylhydantoin, trihaloisocyanuric acid, and sodium dihaloisocyanurate.

10 . The method of claim 6 , wherein said oxidative agent is sodium chlorite.

11 . A method of treating a disease associated with migration of activated macrophages, said method comprising administering a therapeutically-effective amount of an oxidative agent to a subject in need thereof, wherein said oxidative agent is selected from the group consisting of non-halogen activated-oxygen compounds, non-oxygen activated-halogen compounds, activated-halogen activated-oxygen compounds, and N-halo compounds.

12 . The method of claim 11 , wherein

i) the non-halogen activated-oxygen compounds are selected from potassium nitrate (KNO 3 ), permanganate salts, ammonium cerium(IV) nitrate, hexavalent chromium compounds, chromate/dichromate compounds, ammonium silver nitrate, sulfoxides, persulfuric acid, osmium tetroxide (OsO 4 ), nitric acid, nitrous oxide (N 2 O), hydrogen peroxide, organic peroxides, superoxides, and ozone;

ii) the non-oxygen activated-halogen compounds are selected from fluorine, chlorine, bromine, and iodine;

iii) the activated-halogen activated-oxygen compounds are selected from sodium chlorite and tetrachlorodecaoxygen; and

iv) the N-halo compounds are selected from the group consisting of N-halophthalimide, N-halosuccinimide, N-halosaccharin, N,N-dihalourethane, N-haloacetanilide, 1,3-dihalo-5,5-dimethylhydantoin, trihaloisocyanuric acid, and sodium dihaloisocyanurate.

13 . The method of claim 11 , wherein said oxidative agent is sodium chlorite.

14 . A method of treating a disease associated with excess activation of monocytes to activated macrophages, said method comprising administering a therapeutically-effective amount of an oxidative agent to a subject in need thereof, wherein said oxidative agent is selected from the group consisting of non-halogen activated-oxygen compounds, non-oxygen activated-halogen compounds, and N-halo compounds.

15 . The method of claim 14 , wherein

i) the non-halogen activated-oxygen compounds are selected from potassium nitrate (KNO 3 ), permanganate salts, ammonium cerium(IV) nitrate, hexavalent chromium compounds, chromate/dichromate compounds, ammonium silver nitrate, sulfoxides, persulfuric acid, osmium tetroxide (OsO 4 ), nitric acid, nitrous oxide (N 2 O), hydrogen peroxide, organic peroxides, superoxides, and ozone;

ii) the non-oxygen activated-halogen compounds are selected from fluorine, chlorine, bromine, and iodine; and

iii) the N-halo compounds are selected from the group consisting of N-halophthalimide, N-halosuccinimide, N-halosaccharin, N,N-dihalourethane, N-haloacetanilide, 1,3-dihalo-5,5-dimethylhydantoin, trihaloisocyanuric acid, and sodium dihaloisocyanurate.

16 . The method of claim 14 , wherein said oxidative agent is selected from 1,3-dichloro-5,5-dimethylhydantoin and chloramine-T.

17 . The method of claim 14 , wherein said disease is associated with excess CD14CD16 expression.

18 . The method of claim 14 , wherein said disease is a neurodegenerative disease selected from the group consisting of amyotrophic lateral sclerosis (ALS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and complications thereof.

19 . A sodium chlorite compound, wherein said compound is a crystalline solid of greater than 95% purity.

20 . The compound of claim 19 , wherein said compound is a crystalline solid of greater than 99% purity.

21 . The compound of claim 19 , wherein said compound has an x-ray powder diffraction pattern with peaks expressed in degrees 20 at about 21, 30, 31, 32, 34, and 39.

22 . A pharmaceutical composition comprising one or more pharmaceutical excipients and the compound of claim 19 , wherein said composition is a solid.

23 . A pharmaceutical composition comprising:

(a) the compound of claim 19 ;

(b) a pH adjusting agent; and

(c) a pharmaceutically acceptable excipient or carrier,

wherein said composition is a liquid that exhibits 25% less pH drift compared to an identical composition without said pH adjusting agent.

24 . The composition of claim 23 , wherein said pH adjusting agent is sodium phosphate dibasic.

25 . A method of treating Type II diabetes or related complications comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising chlorite or a chlorite-containing agent.

26 . A method of treating a disease associated with migration of monocytes or activated macrophages, said method comprising administering a therapeutically-effective amount of an oxidative agent to a subject in need thereof, wherein said oxidative agent is selected from the group consisting of non-halogen activated-oxygen compounds, non-oxygen activated-halogen compounds, activated-halogen activated-oxygen compounds, and N-halo compounds.

27 . The method of claim 26 , wherein said disease is characterized by elevated CD16 expression levels in CD14+ cells.

28 . The method of claim 27 , wherein said oxidative agent is selected from sodium chlorite, 1,3-dichloro-5,5-dimethylhydantoin and chloramine-T.

29 . The method of claim 26 , wherein said disease is characterized by migration of PBMCs in response to chemoattractant.

30 . The method of claim 29 , wherein said oxidative agent is sodium chlorite.

31 . A method of treating a disease associated with excess production of sCD14 and/or sCD163 by activated macrophages, said method comprising administering a therapeutically-effective amount of an oxidative agent to a subject in need thereof, wherein said oxidative agent is selected from the group consisting of non-halogen activated-oxygen compounds, non-oxygen activated-halogen compounds, activated-halogen activated-oxygen compounds, and N-halo compounds.

32 . The method of claim 31 , wherein said oxidative agent is sodium chlorite.

33 . A method of diagnosing a macrophage related disease in a subject comprising measuring the level of a biomarker in the subject and correlating the measured level of biomarker to normal and diseased levels of said biomarker, wherein said biomarker is selected from CD16 expression in CD14+ cells, sCD14, sCD163, expression of chemoattractants by macrophages, and combinations thereof.

34 . A method of determining efficacy of treatment with an oxidative agent for a macrophage related disease in a subject comprising:

i) initiating treatment with an oxidative agent;

ii) measuring the level of a biomarker in the subject; and

iii) correlating the measured level of biomarker to normal and diseased levels of said biomarker and/or levels of biomarker in said subject prior to treatment;

wherein said biomarker is selected from CD16 expression in CD14+ cells, sCD14, sCD163, expression of chemoattractants by macrophages, and combinations thereof.

35 . The method of claim 34 , wherein said oxidative treatment is sodium chlorite.