Novel adjunctive therapies for the treatment of tuberculosis

Current Molecular Medicine

Volumn 14, Issue 3, 2014, Pages 385-395

  Ordonez, A A ^a   Maiga, M ^a   Gupta, S ^a   Weinstein, E A ^a   Bishai, W R ^a   Jain, S K ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Corticosteroids; Efflux pump inhibitors; Inflammation; Microenvironment; TNF

Indexed keywords

ADALIMUMAB; AMINOSALICYLIC ACID; CORTICOSTEROID; CORTICOTROPIN; DEXAMETHASONE; ETANERCEPT; ISONIAZID; MATRIX METALLOPROTEINASE; METHYLPREDNISOLONE; NIVOLUMAB; PENTOXIFYLLINE; PHENOTHIAZINE DERIVATIVE; PHOSPHODIESTERASE INHIBITOR; PREDNISOLONE; PREDNISONE; PYRAZINAMIDE; RIFAMPICIN; ROFLUMILAST; SILDENAFIL; STREPTOMYCIN; TADALAFIL; THALIDOMIDE; THIORIDAZINE; TUBERCULOSTATIC AGENT; TUMOR NECROSIS FACTOR ALPHA INHIBITOR;

ADJUVANT THERAPY; DELAYED HYPERSENSITIVITY; GRANULOMA; HUMAN; LUNG ALVEOLUS MACROPHAGE; LUNG LESION; LUNG TUBERCULOSIS; MICROENVIRONMENT; MIXED INFECTION; MULTIDRUG RESISTANT TUBERCULOSIS; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PNEUMOCYSTIS PNEUMONIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STEROID THERAPY; TUBERCULOSIS; TUBERCULOUS MENINGITIS; TUBERCULOUS PLEURISY; BIOLOGICAL MODEL; METABOLISM;

ADRENAL CORTEX HORMONES; HUMANS; MODELS, BIOLOGICAL; TUBERCULOSIS;

EID: 84897458313     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/1566524013666131118112431     Document Type: Review

References (138)

1. WHO. Global tuberculosis report 2013. Accessed: November 28, 2013; Available from: http://apps. who. int/iris/bitstream/10665/91355/1/9789241564 656_eng. pdf.
2. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999; 282(7): 677-86.
3. Stead WW. Pathogenesis of a first episode of chronic pulmonary tuberculosis in man: recrudescence of residuals of the primary infection or exogenous reinfection? Am Rev Respir Dis 1967; 95(5): 729-45.
4. Podlekareva DN, Panteleev AM, Grint D, et al. Short and long term mortality and causes of death in HIV/TB patients in Europe. Eur Respir J 2013; epub ahead of print.
5. Grosset JH, Singer TG, Bishai WR. New drugs for the treatment of tuberculosis: hope and reality. Int J Tuberc Lung Dis 2012; 16(8): 1005-14.
6. Churchyard G, Onyebujoh P, Zumla A, et al. World Health Organization. WHO-Special Programme for Research and Training in Tropical Diseases: 2007.
7. Szumowski JD, Adams KN, Edelstein PH, Ramakrishnan L. Antimicrobial Efflux Pumps and Mycobacterium Tuberculosis Drug Tolerance: Evolutionary Considerations. Curr Top Microbiol Immunol 2012; epub ahead of print.
8. Gomez JE, McKinney JD. M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis (Edinb) 2004; 84(1-2): 29-44.
9. Vandiviere HM, Loring WE, Melvin I, Willis S. The treated pulmonary lesion and its tubercle bacillus. II. The death and resurrection. Am J Med Sci 1956; 232(1): 30-7; passim.
10. Haapanen JH, Kass I, Gensini G, Middlebrook G. Studies on the gaseous content of tuberculous cavities. Am Rev Respir Dis 1959; 80(1, Part 1): 1-5.
11. Lillebaek T, Dirksen A, Vynnycky E, et al. Stability of DNA patterns and evidence of Mycobacterium tuberculosis reactivation occurring decades after the initial infection. J Infect Dis 2003; 188(7): 1032-9.
12. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347(20): 1549-56.
13. van de Beek D, de Gans J, McIntyre P, Prasad K. Steroids in adults with acute bacterial meningitis: a systematic review. Lancet Infect Dis 2004; 4(3): 139-43.
14. McIntyre PB, Berkey CS, King SM, et al. Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988. JAMA 1997; 278(11): 925-31.
15. Gilroy SA, Bennett NJ. Pneumocystis pneumonia. Semin Respir Crit Care Med 2011; 32(6): 775-82.
16. Spagnolo P, Fabbri LM, Bush A. Long-term macrolide treatment for chronic respiratory disease. Eur Respir J 2012; 42(1): 239-251.
17. Annane D. Corticosteroids for severe sepsis: an evidencebased guide for physicians. Ann Intensive Care 2011; 1(1): 7.
18. De Bosscher K, Haegeman G, Elewaut D. Targeting inflammation using selective glucocorticoid receptor modulators. Curr Opin Pharmacol 2010; 10(4): 497-504.
19. Meagher LC, Cousin JM, Seckl JR, Haslett C. Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol 1996; 156(11): 4422-8.
20. Sternberg EM. Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat Rev Immunol 2006; 6(4): 318-28.
21. Stahn C, Buttgereit F. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol 2008; 4(10): 525-33.
22. Capon AW. ACTH, cortisone and tuberculosis. Can Med Assoc J 1952; 67(1): 46-8.
23. Reale M, Garaventa A, Paoli G, Costa G. Prednisone and prednisolone, anti-reactive elective drugs in pulmonary tuberculosis. Minerva Med 1956; 47(45): 1764-73.
24. Heyman A, Levitzky E. Steroids in the treatment of childhood tuberculosis. J Med Soc N J 1959; 56(2): 62-7.
25. Lavers KW, Roberts JC. The use of prednisone in primary tuberculosis in children. Tubercle 1959; 40: 173-6.
26. Handley AE. The use of corticosteroids in combination with isonicotinic acid hydrazide in the treatment of advanced bilateral progressive cavitary pulmonary tuberculosis; second report with discussion. S Afr Med J 1956; 30(52): 1250-1.
27. Horne NW. Prednisolone in treatment of pulmonary tuberculosis: a controlled trial. Final report to the Research Committee of the Tuberculosis Society of Scotland. Br Med J 1960; 2(5215): 1751-6.
28. Morris D. Trial of Corticotrophin and Prednisone with Chemotherapy in Pulmonary Tuberculosis: A Two-Year Radiographic Follow-Up. Tubercle 1963; 44: 484-6.
29. El-Dewi T, Bonstein H, Favez G. Comparative effects of prednisone and dexamethasone (associated with bacteriostatics) in the clinical course and plasma parameters in pulmonary tuberculosis patients. Schweiz Med Wochenschr 1962; 92: 1398-403.
30. Bornstein PK, Nair KG, Epstein IG. Reduction of chronicity in pulmonary tuberculosis by prednisone. Am Rev Respir Dis 1960; 81: 421-2.
31. Chatterjee PK, Goswami PN, Chatterjee SC, Das SK. Prednisone in small doses in the treatment of tuberculosis. J Indian Med Assoc 1958; 31(6): 233-8.
32. Dooley DP, Carpenter JL, Rademacher S. Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature. Clin Infect Dis 1997; 25(4): 872-87.
33. Smego RA, Ahmed N. A systematic review of the adjunctive use of systemic corticosteroids for pulmonary tuberculosis. Int J Tuberc Lung Dis 2003; 7(3): 208-13.
34. Tuberculosis Research Centre. Study of chemotherapy regimens of 5 and 7 months' duration and the role of corticosteroids in the treatment of sputum-positive patients with pulmonary tuberculosis in South India. Tubercle 1983; 64(2): 73-91.
35. Bilaceroglu S, Perim K, Buyuksirin M, Celikten E. Prednisolone: a beneficial and safe adjunct to antituberculosis treatment? A randomized controlled trial. Int J Tuberc Lung Dis 1999; 3(1): 47-54.
36. Mayanja-Kizza H, Jones-Lopez E, Okwera A, et al. Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: a phase 2 clinical trial in Uganda. J Infect Dis 2005; 191(6): 856-65.
37. Meintjes G, Wilkinson RJ, Morroni C, et al. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS 2010; 24(15): 2381-90.
38. Meintjes G, Skolimowska KH, Wilkinson KA, et al. Corticosteroid-modulated immune activation in the tuberculosis immune reconstitution inflammatory syndrome. Am J Respir Crit Care Med 2012; 186(4): 369-77.
39. Conesa-Botella A, Meintjes G, Coussens AK, et al. Corticosteroid therapy, vitamin D status, and inflammatory cytokine profile in the HIV-tuberculosis immune reconstitution inflammatory syndrome. Clin Infect Dis 2012; 55(7): 1004-11.
40. Escobar JA, Belsey MA, Duenas A, Medina P. Mortality from tuberculous meningitis reduced by steroid therapy. Pediatrics 1975; 56(6): 1050-5.
41. Schoeman JF, Van Zyl LE, Laubscher JA, Donald PR. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Pediatrics 1997; 99(2): 226-31.
42. Be NA, Kim KS, Bishai WR, Jain SK. Pathogenesis of central nervous system tuberculosis. Curr Mol Med 2009; 9(2): 94-9.
43. Girgis NI, Farid Z, Kilpatrick ME, Sultan Y, Mikhail IA. Dexamethasone adjunctive treatment for tuberculous meningitis. Pediatr Infect Dis J 1991; 10(3): 179-83.
44. Thwaites GE, Nguyen DB, Nguyen HD, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med 2004; 351(17): 1741-51.
45. Torok ME, Nguyen DB, Tran TH, et al. Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents. PLoS One 2011; 6(12): e27821.
46. Ruslami R, Ganiem AR, Dian S, et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis 2013; 13(1): 27-35.
47. Prasad K, Singh MB. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev 2008; (1): CD002244.
48. Malhotra HS, Garg RK, Singh MK, Agarwal A, Verma R. Corticosteroids (dexamethasone versus intravenous methylprednisolone) in patients with tuberculous meningitis. Ann Trop Med Parasitol 2009; 103(7): 625-34.
49. Tobin DM, Roca FJ, Oh SF, et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell 2012; 148(3): 434-46.
50. Afghani B, Lieberman JM. Paradoxical enlargement or development of intracranial tuberculomas during therapy: case report and review. Clin Infect Dis 1994; 19(6): 1092-9.
51. Jain SK, Kwon P, Moss WJ. Management and outcomes of intracranial tuberculomas developing during antituberculous therapy: case report and review. Clin Pediatr (Phila) 2005; 44(5): 443-50.
52. Kaojarern S, Supmonchai K, Phuapradit P, Mokkhavesa C, Krittiyanunt S. Effect of steroids on cerebrospinal fluid penetration of antituberculous drugs in tuberculous meningitis. Clin Pharmacol Ther 1991; 49(1): 6-12.
53. Thwaites G, Fisher M, Hemingway C, et al. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect 2009; 59(3): 167-87.
54. Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 2003; 167(4): 603-62.
55. Lee CH, Wang WJ, Lan RS, Tsai YH, Chiang YC. Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study. Chest 1988; 94(6): 1256-9.
56. Elliott AM, Luzze H, Quigley MA, et al. A randomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis. J Infect Dis 2004; 190(5): 869-78.
57. Engel ME, Matchaba PT, Volmink J. Corticosteroids for tuberculous pleurisy. Cochrane Database Syst Rev 2007; (4): CD001876.
58. Hakim JG, Ternouth I, Mushangi E, et al. Double blind randomised placebo controlled trial of adjunctive prednisolone in the treatment of effusive tuberculous pericarditis in HIV seropositive patients. Heart 2000; 84(2): 183-8.
59. Mayosi BM, Volmink JA, Commerford PJ. Interventions for treating tuberculous pericarditis. Cochrane Database Syst Rev 2000; (2): CD000526.
60. Mootoo A, Stylianou E, Arias MA, Reljic R. TNF-alpha in tuberculosis: a cytokine with a split personality. Inflamm Allergy Drug Targets 2009; 8(1): 53-62.
61. Keane J, Balcewicz-Sablinska MK, Remold HG, et al. Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis. Infect Immun 1997; 65(1): 298-304.
62. Mohan VP, Scanga CA, Yu K, et al. Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis: possible role for limiting pathology. Infect Immun 2001; 69(3): 1847-55.
63. Flynn JL, Chan J. What's good for the host is good for the bug. Trends Microbiol 2005; 13(3): 98-102.
64. Ramakrishnan L. Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol 2012; 12(5): 352-66.
65. Skerry C, Harper J, Klunk M, Bishai WR, Jain SK. Adjunctive TNF inhibition with standard treatment enhances bacterial clearance in a murine model of necrotic TB granulomas. PLoS One 2012; 7(6): e39680.
66. Roca FJ, Ramakrishnan L. TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell 2013; 153(3): 521-34.
67. Agarwal N, Lamichhane G, Gupta R, Nolan S, Bishai WR. Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase. Nature 2009; 460(7251): 98-102.
68. Tsenova L, Sokol K, Freedman VH, Kaplan G. A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death. J Infect Dis 1998; 177(6): 1563-72.
69. Schoeman JF, Springer P, van Rensburg AJ, et al. Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study. J Child Neurol 2004; 19(4): 250-7.
70. Guo S, Zhao J. Immunotherapy for tuberculosis: what's the better choice? Front Biosci 2012; 17: 2684-90.
71. Tsenova L, Mangaliso B, Muller G, et al. Use of IMiD3, a thalidomide analog, as an adjunct to therapy for experimental tuberculous meningitis. Antimicrob Agents Chemother 2002; 46(6): 1887-95.
72. Koo MS, Manca C, Yang G, et al. Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice. PLoS One 2011; 6(2): e17091.
73. Maiga M, Agarwal N, Ammerman NC, et al. Successful Shortening of Tuberculosis Treatment Using Adjuvant Host-Directed Therapy with FDA-Approved Phosphodiesterase Inhibitors in the Mouse Model. PLoS One 2012; 7(2): e30749.
74. Subbian S, Tsenova L, O'Brien P, et al. Phosphodiesterase-4 inhibition combined with isoniazid treatment of rabbits with pulmonary tuberculosis reduces macrophage activation and lung pathology. Am J Pathol 2011; 179(1): 289-301.
75. Subbian S, Tsenova L, O'Brien P, et al. Phosphodiesterase-4 inhibition alters gene expression and improves isoniazidmediated clearance of Mycobacterium tuberculosis in rabbit lungs. PLoS Pathog 2011; 7(9): e1002262.
76. Wallis RS, Kyambadde P, Johnson JL, et al. A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis. AIDS 2004; 18(2): 257-64.
77. Wallis RS, van Vuuren C, Potgieter S. Adalimumab treatment of life-threatening tuberculosis. Clin Infect Dis 2009; 48(10): 1429-32.
78. Bekker LG, Maartens G, Steyn L, Kaplan G. Selective increase in plasma tumor necrosis factor-alpha and concomitant clinical deterioration after initiating therapy in patients with severe tuberculosis. J Infect Dis 1998; 178(2): 580-4.
79. Wallis RS. Reconsidering adjuvant immunotherapy for tuberculosis. Clin Infect Dis 2005; 41(2): 201-8.
80. Blackmore TK, Manning L, Taylor WJ, Wallis RS. Therapeutic use of infliximab in tuberculosis to control severe paradoxical reaction of the brain and lymph nodes. Clin Infect Dis 2008; 47(10): e83-5.
81. Wallis RS, Kyambadde P, Johnson JL, et al. A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis. AIDS 2004; 18(2): 257-264.
82. Pan H, Yan BS, Rojas M, et al. Ipr1 gene mediates innate immunity to tuberculosis. Nature 2005; 434(7034): 767-72.
83. Harper J, Skerry C, Davis SL, et al. Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. J Infect Dis 2012; 205(4): 595-602.
84. Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690, 550 versus placebo. Arthritis Rheum 2009; 60(7): 1895-905.
85. Sweeny DJ, Li W, Clough J, et al. Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation. Drug Metab Dispos 2010; 38(7): 1166-76.
86. Johannessen M, Moens U. Multisite phosphorylation of the cAMP response element-binding protein (CREB) by a diversity of protein kinases. Front Biosci 2007; 12: 1814-32.
87. Omori K, Kotera J. Overview of PDEs and their regulation. Circ Res 2007; 100(3): 309-27.
88. Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alphaneutralizing agent. N Engl J Med 2001; 345(15): 1098-104.
89. Centers for Disease Control and Prevention (CDC). Tuberculosis associated with blocking agents against tumor necrosis factor-alpha--California, 2002-2003. MMWR Morb Mortal Wkly Rep 2004; 53(30): 683-6.
90. Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004; 38(9): 1261-5.
91. Izzo AA, Izzo LS, Kasimos J, Majka S. A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of Mycobacterium tuberculosis pulmonary infection. Tuberculosis (Edinb) 2004; 84(6): 387-96.
92. Taylor JL, Hattle JM, Dreitz SA, et al. Role for matrix metalloproteinase 9 in granuloma formation during pulmonary Mycobacterium tuberculosis infection. Infect Immun 2006; 74(11): 6135-44.
93. Elkington PT, Friedland JS. Matrix metalloproteinases in destructive pulmonary pathology. Thorax 2006; 61(3): 259-66.
94. Green JA, Elkington PT, Pennington CJ, et al. Mycobacterium tuberculosis upregulates microglial matrix metalloproteinase-1 and-3 expression and secretion via NFkappaB-and Activator Protein-1-dependent monocyte networks. J Immunol 2010; 184(11): 6492-503.
95. Walker NF, Clark SO, Oni T, et al. Doxycycline and HIV infection suppress tuberculosis-induced matrix metalloproteinases. Am J Respir Crit Care Med 2012; 185(9): 989-97.
96. Zasloff M. Fighting infections with vitamin D. Nat Med 2006; 12(4): 388-90.
97. Chun RF, Adams JS, Hewison M. Immunomodulation by vitamin D: implications for TB. Expert Rev Clin Pharmacol 2011; 4(5): 583-91.
98. Gibney KB, MacGregor L, Leder K, et al. Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clin Infect Dis 2008; 46(3): 443-6.
99. Williams B, Williams AJ, Anderson ST. Vitamin D deficiency and insufficiency in children with tuberculosis. Pediatr Infect Dis J 2008; 27(10): 941-2.
100. Wejse C, Olesen R, Rabna P, et al. Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls. Am J Clin Nutr 2007; 86(5): 1376-83.
101. Ustianowski A, Shaffer R, Collin S, Wilkinson RJ, Davidson RN. Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London. J Infect 2005; 50(5): 432-7.
102. Sasidharan PK, Rajeev E, Vijayakumari V. Tuberculosis and vitamin D deficiency. J Assoc Physicians India 2002; 50: 554-8.
103. Martineau AR, Wilkinson KA, Newton SM, et al. IFN-gammaand TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol 2007; 178(11): 7190-8.
104. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol 2010; 10(4): 482-96.
105. Hewison M. Antibacterial effects of vitamin D. Nat Rev Endocrinol 2011; 7(6): 337-45.
106. Chen S, Sims GP, Chen XX, Gu YY, Lipsky PE. Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 2007; 179(3): 1634-47.
107. Rockett KA, Brookes R, Udalova I, et al. 1, 25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect Immun 1998; 66(11): 5314-21.
108. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311(5768): 1770-3.
109. Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol 2007; 179(4): 2060-3.
110. Di Nardo A, Vitiello A, Gallo RL. Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol 2003; 170(5): 2274-8.
111. Agerberth B, Charo J, Werr J, et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 2000; 96(9): 3086-93.
112. Nursyam EW, Amin Z, Rumende CM. The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med Indones 2006; 38(1): 3-5.
113. Coussens AK, Wilkinson RJ, Hanifa Y, et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci U S A 2012; 109(38): 15449-54.
114. Martineau AR, Timms PM, Bothamley GH, et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 2011; 377(9761): 242-50.
115. Wejse C, Gomes VF, Rabna P, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2009; 179(9): 843-50.
116. Lazar-Molnar E, Chen B, Jacobs W, Nathenson S. Inhibition through PD-1 is crucial for protection against M. tuberculosis infection. J Immunol 2011; 186: (Meeting Abstract Supplement) 58. 1.
117. Lazar-Molnar E, Chen B, Sweeney KA, et al. Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis. Proc Natl Acad Sci U S A 2010; 107(30): 13402-7.
118. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443-54.
119. Azuma A. Pirfenidone treatment of idiopathic pulmonary fibrosis. Ther Adv Respir Dis 2012; 6(2): 107-14.
120. Azuma A. Pirfenidone: antifibrotic agent for idiopathic pulmonary fibrosis. Expert Rev Respir Med 2010; 4(3): 301-10.
121. Gold B, Pingle M, Brickner SJ, et al. Nonsteroidal antiinflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials. Proc Natl Acad Sci U S A 2012; 109(40): 16004-11.
122. Moitra K, Lou H, Dean M. Multidrug efflux pumps and cancer stem cells: insights into multidrug resistance and therapeutic development. Clin Pharmacol Ther 2011; 89(4): 491-502.
123. Amaral L, Engi H, Viveiros M, Molnar J. Comparison of multidrug resistant efflux pumps of cancer and bacterial cells with respect to the same inhibitory agents. In Vivo 2007; 21(2): 237-44.
124. Tegos GP, Haynes M, Strouse JJ, et al. Microbial efflux pump inhibition: tactics and strategies. Curr Pharm Des 2011; 17(13): 1291-302.
125. Adams KN, Takaki K, Connolly LE, et al. Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell 2011; 145(1): 39-53.
126. Balganesh M, Dinesh N, Sharma S, et al. Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates. Antimicrob Agents Chemother 2012; 56(5): 2643-51.
127. Schmalstieg AM, Srivastava S, Belkaya S, et al. The antibiotic resistance arrow of time: efflux pump induction is a general first step in the evolution of mycobacterial drug resistance. Antimicrob Agents Chemother 2012; 56(9): 4806-15.
128. Louw GE, Warren RM, Gey van Pittius NC, et al. Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux. Am J Respir Crit Care Med 2011; 184(2): 269-76.
129. Amaral L, Viveiros M. Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections. Int J Antimicrob Agents 2012; 39(5): 376-80.
130. Ordway D, Viveiros M, Leandro C, et al. Clinical concentrations of thioridazine kill intracellular multidrugresistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 2003; 47(3): 917-22.
131. Weinstein EA, Yano T, Li LS, et al. Inhibitors of type II NADH: menaquinone oxidoreductase represent a class of antitubercular drugs. Proc Natl Acad Sci U S A 2005; 102(12): 4548-53.
132. Martins M, Viveiros M, Couto I, Amaral L. Targeting human macrophages for enhanced killing of intracellular XDR-TB and MDR-TB. Int J Tuberc Lung Dis 2009; 13(5): 569-73.
133. Udwadia ZF, Sen T, Pinto LM. Safety and efficacy of thioridazine as salvage therapy in Indian patients with XDRTB. Recent Pat Antiinfect Drug Discov 2011; 6(2): 88-91.
134. Abbate E, Vescovo M, Natiello M, et al. Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and thioridazine. J Antimicrob Chemother 2012; 67(2): 473-7.
135. Huang T-S, Kunin CM, Wang H-M, et al. Inhibition of the Mycobacterium tuberculosis reserpine-sensitive efflux pump augments intracellular concentrations of ciprofloxacin and enhances susceptibility of some clinical isolates. Journal of the Formosan Medical Association 2012; in press.
136. Escribano I, Rodriguez C, Llorca B, et al. Importance of the efflux pump systems in the resistance of Mycobacterium tuberculosis to Fluoroquinolones and linezolid. Chemotherapy 2007; 53(6): 397-401.
137. Sunila ES, Kuttan, G. Immunomodulatory and antitumor activity of Piper longum Linn. and piperine. J Ethnopharmacol 2004; 90(2-3): 339-46.
138. Sharma S, Kumar M, Nargotra A, Koul S, Khan IA. Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis. J Antimicrob Chemother 2010; 65(8): 1694-701.