{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T23:49:27Z","timestamp":1777333767656,"version":"3.51.4"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"DOI":"10.3389\/fcimb.2019.00450","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T14:28:01Z","timestamp":1579012081000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Thalidomide and Phosphodiesterase 4 Inhibitors as Host Directed Therapeutics for Tuberculous Meningitis: Insights From the Rabbit Model"],"prefix":"10.3389","volume":"9","author":[{"given":"Ranjeet","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afsal","family":"Kolloli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pooja","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Vinnard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilla","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selvakumar","family":"Subbian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/nrc1323","article-title":"The evolution of thalidomide and its IMiD derivatives as anticancer agents","volume":"4","author":"Bartlett","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e11186","DOI":"10.1097\/MD.0000000000011186","article-title":"Intracranial tuberculous mass lesions treated with thalidomide in an immunocompetent child from a low tuberculosis endemic country: a case report","volume":"97","author":"Caraffa","year":"2018","journal-title":"Medicine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"I107","DOI":"10.1136\/ard.58.2008.i107","article-title":"Immunomodulation by thalidomide and thalidomide analogues","volume":"58","author":"Corral","year":"1999","journal-title":"Ann. Rheum. Dis."},{"key":"B4","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/BF03401909","article-title":"Selection of novel analogues of thalidomide with enhanced TNF-\u03b1 inhibitory activity","volume":"2","author":"Corral","year":"1996","journal-title":"Mol. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.neuint.2003.08.012","article-title":"Inhibition of cytokines expression in human microglia infected by virulent and non-virulent mycobacteria","volume":"44","author":"Curto","year":"2004","journal-title":"Neurochem. Int."},{"key":"B6","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0033-8389(22)00616-9","article-title":"Pathology and pathogenetic mechanisms in neurotuberculosis","volume":"33","author":"Dastur","year":"1995","journal-title":"Radiol. Clin. North Am."},{"key":"B7","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/JLB.MR0318-102R","article-title":"The pathogenesis of tuberculous meningitis","volume":"105","author":"Davis","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1093\/clinids\/21.4.924","article-title":"Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis","volume":"21","author":"Donald","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/0002-9343(92)90579-Z","article-title":"Tuberculous meningitis in patients with and without human immunodeficiency virus infection","volume":"93","author":"Dube","year":"1992","journal-title":"Am. J. Med."},{"key":"B10","doi-asserted-by":"crossref","first-page":"20436","DOI":"10.2807\/ese.18.12.20436-en","article-title":"The burden of extrapulmonary and meningitis tuberculosis: an investigation of national surveillance data, Germany, 2002 to 2009","volume":"18","author":"Ducomble","year":"2013","journal-title":"Euro Surveill."},{"key":"B11","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1093\/oxfordjournals.aje.a112675","article-title":"Extrapulmonary tuberculosis in the United States","volume":"109","author":"Farer","year":"1979","journal-title":"Am. J. Epidemiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jns.2014.03.025","article-title":"Paradoxical reaction in HIV negative tuberculous meningitis","volume":"340","author":"Garg","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1136\/pmj.79.929.127","article-title":"Thalidomide and its derivatives: emerging from the wilderness","volume":"79","author":"Gordon","year":"2003","journal-title":"Postgrad. Med. J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1084\/jem.187.11.1885","article-title":"Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset","volume":"187","author":"Haslett","year":"1998","journal-title":"J. Exp. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1089\/088922299310269","article-title":"Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients","volume":"15","author":"Haslett","year":"1999","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1086\/498216","article-title":"Effective treatment of erythema nodosum leprosum with thalidomide is associated with immune stimulation","volume":"192","author":"Haslett","year":"2005","journal-title":"J. Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1056\/NEJMoa1507062","article-title":"Intensified antituberculosis therapy in adults with tuberculous meningitis","volume":"374","author":"Heemskerk","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1001\/archpedi.1924.01920110009002","article-title":"The Production of tuberculous meningitis in the rabbit and the changes in its cerebrospinal fluid","volume":"27","author":"Kasahara","year":"1924","journal-title":"Am. J. Dis. Child."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1111\/ene.13732","article-title":"Clinical perspectives into the use of thalidomide for central nervous system tuberculosis","volume":"25","author":"Keddie","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"22382","DOI":"10.1074\/jbc.M100938200","article-title":"Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity","volume":"276","author":"Keifer","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1111\/j.1476-5381.2011.01729.x","article-title":"Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments","volume":"165","author":"Keravis","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0121725","DOI":"10.1371\/journal.pone.0121725","article-title":"The unrecognized effects of phosphodiesterase 4 on epithelial cells in pulmonary inflammation","volume":"10","author":"Konrad","year":"2015","journal-title":"PLoS ONE"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e17091","DOI":"10.1371\/journal.pone.0017091","article-title":"Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice","volume":"6","author":"Koo","year":"2011","journal-title":"PLoS ONE"},{"key":"B24","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.tube.2010.08.005","article-title":"The mechanisms and consequences of the extra-pulmonary dissemination of Mycobacterium tuberculosis","volume":"90","author":"Krishnan","year":"2010","journal-title":"Tuberculosis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/S1473-3099(10)70138-9","article-title":"Tuberculous meningitis: a uniform case definition for use in clinical research","volume":"10","author":"Marais","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1517\/14712598.1.4.675","article-title":"Immunotherapeutic and antitumour potential of thalidomide analogues","volume":"1","author":"Marriott","year":"2001","journal-title":"Expert Opin. Biol. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nrd4228","article-title":"Advances in targeting cyclic nucleotide phosphodiesterases","volume":"13","author":"Maurice","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1016\/j.biocel.2007.01.022","article-title":"The thalidomide saga","volume":"39","author":"Melchert","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.molmed.2017.02.006","article-title":"A brighter side to thalidomide: its potential use in immunological disorders","volume":"23","author":"Millrine","year":"2017","journal-title":"Trends Mol. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jns.2010.03.025","article-title":"Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial","volume":"293","author":"Misra","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1084\/jem.177.6.1675","article-title":"Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation","volume":"177","author":"Moreira","year":"1993","journal-title":"J. Exp. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1016\/s0960-894x(99)00250-4","article-title":"Amino-substituted thalidomide analogues: potent inhibitors of TNF-\u03b1 production","volume":"9","author":"Muller","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3238","DOI":"10.1021\/jm9603328","article-title":"Structural modifications of thalidomide produce analogs with enhanced TNF inhibitory activity","volume":"39","author":"Muller","year":"1996","journal-title":"J. Med. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1056\/NEJMoa070852","article-title":"Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis","volume":"357","author":"Nguyen","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"CD002244","DOI":"10.1002\/14651858.CD002244.pub4","article-title":"Corticosteroids for managing tuberculous meningitis","volume":"4","author":"Prasad","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"B36","first-page":"5","article-title":"The pathogenesis of tuberculous meningitis","volume":"52","author":"Rich","year":"1933","journal-title":"Bull. John Hopkins Hosp."},{"key":"B37","doi-asserted-by":"publisher","first-page":"993","DOI":"10.4103\/0028-3886.266232","article-title":"Role of aspirin in tuberculous meningitis: a systematic review and meta-analysis","volume":"67","author":"Rizvi","year":"2019","journal-title":"Neurol. India"},{"key":"B38","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0163-4453(03)00077-X","article-title":"The use of thalidomide in the treatment of intracranial tuberculomas in adults: two case reports","volume":"47","author":"Roberts","year":"2003","journal-title":"J. Infect."},{"key":"B39","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1128\/CMR.00042-07","article-title":"Central nervous system tuberculosis: pathogenesis and clinical aspects","volume":"21","author":"Rock","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1093\/infdis\/168.2.408","article-title":"The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum","volume":"168","author":"Sampaio","year":"1993","journal-title":"J. Infect. Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1084\/jem.173.3.699","article-title":"Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes","volume":"173","author":"Sampaio","year":"1991","journal-title":"J. Exp. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1177\/0883073809350507","article-title":"Tuberculous meningitis-related optic neuritis: recovery of vision with thalidomide in 4 consecutive cases","volume":"25","author":"Schoeman","year":"2010","journal-title":"J. Child Neurol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1177\/0883073811398132","article-title":"The role of aspirin in childhood tuberculous meningitis","volume":"26","author":"Schoeman","year":"2011","journal-title":"J. Child Neurol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1177\/088307380001500801","article-title":"Adjunctive thalidomide therapy of childhood tuberculous meningitis: possible anti-inflammatory role","volume":"15","author":"Schoeman","year":"2000","journal-title":"J. Child Neurol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1177\/088307380401900402","article-title":"Adjunctive thalidomide therapy for childhood tuberculous meningitis: results of a randomized study","volume":"19","author":"Schoeman","year":"2004","journal-title":"J. Child Neurol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1542\/peds.99.2.226","article-title":"Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis","volume":"99","author":"Schoeman","year":"1997","journal-title":"Pediatrics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"238","DOI":"10.3389\/fimmu.2016.00238","article-title":"Pharmacologic inhibition of host phosphodiesterase-4 improves isoniazid-mediated clearance of Mycobacterium tuberculosis","volume":"7","author":"Subbian","year":"","journal-title":"Front. Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.ebiom.2016.01.015","article-title":"Adjunctive phosphodiesterase-4 inhibitor therapy improves antibiotic response to pulmonary tuberculosis in a rabbit model","volume":"4","author":"Subbian","year":"","journal-title":"EBiomedicine"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e1002262","DOI":"10.1371\/journal.ppat.1002262","article-title":"Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs","volume":"7","author":"Subbian","year":"","journal-title":"PLoS Pathog."},{"key":"B50","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ajpath.2011.03.039","article-title":"Phosphodiesterase-4 inhibition combined with isoniazid treatment of rabbits with pulmonary tuberculosis reduces macrophage activation and lung pathology","volume":"179","author":"Subbian","year":"","journal-title":"Am. J. Pathol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1136\/jnnp.68.3.289","article-title":"Tuberculous meningitis","volume":"68","author":"Thwaites","year":"2000","journal-title":"J. Neurol. Neurosurg. Psychiatr."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.1086\/498220","article-title":"The influence of HIV infection on clinical presentation, response to treatment, and outcome in adults with Tuberculous meningitis","volume":"192","author":"Thwaites","year":"2005","journal-title":"J. Infect. Dis."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1056\/NEJMoa040573","article-title":"Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults","volume":"351","author":"Thwaites","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1093\/bmb\/ldv003","article-title":"Tuberculous meningitis: advances in diagnosis and treatment","volume":"113","author":"Torok","year":"2015","journal-title":"Br. Med. Bull."},{"key":"B55","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/BF03401576","article-title":"Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis","volume":"1","author":"Tramontana","year":"1995","journal-title":"Mol. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"5657","DOI":"10.1073\/pnas.96.10.5657","article-title":"Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system","volume":"96","author":"Tsenova","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B57","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1086\/430614","article-title":"Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli","volume":"192","author":"Tsenova","year":"2005","journal-title":"J. Infect. Dis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1128\/IAI.74.4.2392-2401.2006","article-title":"Evaluation of the Mtb72F polyprotein vaccine in a rabbit model of tuberculous meningitis","volume":"74","author":"Tsenova","year":"2006","journal-title":"Infect Immun."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1128\/AAC.46.6.1887-1895.2002","article-title":"Use of IMiD3, a thalidomide analog, as an adjunct to therapy for experimental tuberculous meningitis","volume":"46","author":"Tsenova","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1086\/515327","article-title":"A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death","volume":"177","author":"Tsenova","year":"1998","journal-title":"J. Infect. Dis."},{"key":"B61","doi-asserted-by":"publisher","first-page":"eaau0965","DOI":"10.1126\/scitranslmed.aau0965","article-title":"Noninvasive (11)C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis","volume":"10","author":"Tucker","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1242\/dmm.027326","article-title":"Microglia activation in a pediatric rabbit model of tuberculous meningitis","volume":"9","author":"Tucker","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"B63","doi-asserted-by":"publisher","first-page":"S325","DOI":"10.1093\/infdis\/jis197","article-title":"Adjunct immunotherapies for tuberculosis","volume":"205","author":"Uhlin","year":"2012","journal-title":"J. Infect. Dis."},{"key":"B64","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1038\/s41598-018-36696-3","article-title":"Immune cell characteristics and cytokine responses in adult HIV-negative tuberculous meningitis: an observational cohort study","volume":"9","author":"van Laarhoven","year":"2019","journal-title":"Sci. Rep."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1080\/14656566.2019.1638912","article-title":"Key considerations in the pharmacotherapy of tuberculous meningitis","volume":"20","author":"Wasserman","year":"2019","journal-title":"Expert Opin. Pharmacother."},{"key":"B66","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nrneurol.2017.120","article-title":"Tuberculous meningitis","volume":"13","author":"Wilkinson","year":"2017","journal-title":"Nat. Rev. Neurol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2019.00450\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T07:17:08Z","timestamp":1665472628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2019.00450\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,14]]},"references-count":66,"alternative-id":["10.3389\/fcimb.2019.00450"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2019.00450","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,14]]},"article-number":"450"}}