A combination of a transforming growth factor-beta antagonist and an inhibitor of cyclooxygenase is an effective treatment for murine pulmonary tuberculosis.
Transforming growth factor-beta (TGF-beta) and prostaglandins (PG) regulate the cell-mediated immune response, so it has been proposed that they affect the progression of pulmonary tuberculosis. Here we report that the administration of soluble betaglycan, a potent TGF-beta antagonist, and niflumic acid, a PG synthesis inhibitor, during the chronic phase of experimental murine tuberculosis enhanced Th1 and decreased Th2 cytokines, increased the expression of iNOS and reduced pulmonary inflammation, fibrosis and bacillary load. This immunotherapeutic approach resulted in significant control of the disease comparable to that achieved by anti-microbial treatment alone. Importantly, the combination of immunotherapy and anti-microbials resulted in an accelerated clearance of bacilli from the lung. These results confirm that TGF-beta and PG have a central pathophysiological role in the progression of pulmonary tuberculosis in the mouse and suggest that the addition of immunotherapy to conventional anti-microbial drugs might result in improved treatment of the disease.
Hernández-Pando
R
R
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Departamento de Patología, México City, DF, 04510 México.
Orozco-Esteves
H
H
Maldonado
H A
HA
Aguilar-León
D
D
Vilchis-Landeros
M M
MM
Mata-Espinosa
D A
DA
Mendoza
V
V
López-Casillas
F
F
D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use; D015169:Colony Count, Microbial; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009544:Niflumic Acid / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D011448:Prostaglandin Antagonists / Q000008:administration & dosage / Q000276:immunology; D011509:Proteoglycans / Q000008:administration & dosage* / Q000276:immunology; D018125:Receptors, Transforming Growth Factor beta / Q000008:administration & dosage* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000473:pathology / Q000628:therapy*
D000995:Antitubercular Agents; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D011448:Prostaglandin Antagonists; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan; D009544:Niflumic Acid; D052247:Nitric Oxide Synthase Type II