Monocyte-dependent fibroblast CXCL8 secretion occurs in tuberculosis and limits survival of mycobacteria within macrophages. (33/91)

CXCL8 is a chemokine that is implicated in the formation of tuberculous (TB) granulomas and in immunity to Mycobacterium tuberculosis (Mtb). Fibroblast chemokine secretion is important for modulating inflammatory responses in chronic lung disease and inflammatory arthritis but has not been investigated in the pathophysiology of TB. In this study, we used a cellular model to examine monocyte/macrophage-dependent stimulation of fibroblasts by Mtb in the regulation of chemokine secretion, particularly that of CXCL8. Human lung fibroblasts grown in collagen were stimulated with conditioned medium from Mtb-infected monocytes (CoMTb). CoMTb-induced prolonged dose-dependent, p38-mediated expression of stable CXCL8 mRNA by fibroblasts accompanied by a >10-fold increase in CXCL8 secretion (487 +/- 88 ng/ml vs 48.6 +/- 34 ng/ml in controls) at 120 h. Fibroblasts strongly expressed CXCL8 in vivo in human TB granulomas. Inhibition of TNF-alpha or IL-1 in CoMTb abrogated the induction of CXCL8 at a pretranscriptional level. CXCL8 secretion was NF-kappaB, C/EBP, and JNK dependent. Sustained NF-kappaB activation was demonstrated beyond 24 h in response to CoMTb. Exogenous CXCL8 reduced the survival of Mtb within macrophages, and inhibition of CXCL8 was associated with intracellular mycobacterial proliferation. These data show that fibroblasts have a previously unrecognized role in modulating inflammation in TB by their CXCL8-dependent contribution to cell recruitment and mycobacterial killing within the granuloma.  (+info)

IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. (34/91)

IL-17 is a cytokine that induces neutrophil-mediated inflammation, but its role in protective immunity against intracellular bacterial infection remains unclear. In the present study, we demonstrate that IL-17 is an important cytokine not only in the early neutrophil-mediated inflammatory response, but also in T cell-mediated IFN-gamma production and granuloma formation in response to pulmonary infection by Mycobacterium bovis bacille Calmette-Guerin (BCG). IL-17 expression in the BCG-infected lung was detected from the first day after infection and the expression depended on IL-23. Our observations indicated that gammadelta T cells are a primary source of IL-17. Lung-infiltrating T cells of IL-17-deficient mice produced less IFN-gamma in comparison to those from wild-type mice 4 wk after BCG infection. Impaired granuloma formation was also observed in the infected lungs of IL-17-deficient mice, which is consistent with the decreased delayed-type hypersensitivity response of the infected mice against mycobacterial Ag. These data suggest that IL-17 is an important cytokine in the induction of optimal Th1 response and protective immunity against mycobacterial infection.  (+info)

Massive primary hepatic tuberculoma mimicking hepatocellular carcinoma in an immunocompetent host. (35/91)

Tuberculoma of the liver is rare in an immunocompetent individual. We report a 26-year-old man with upper abdominal pain, abnormal liver function, and raised inflammatory markers. Abdominal computed tomography (CT) scan revealed a mixed attenuation lesion measuring 6 x 5 cm occupying most of the left lobe of the liver. Subsequent histology and culture confirmed tuberculous abscess. Following antituberculous therapy, repeat CT scan revealed complete resolution of the initial findings. This case illustrates the diagnostic difficulties of hepatic tuberculosis (TB) and the importance of considering TB in patients with hepatic lesions.  (+info)

Magnetic resonance spectroscopy in pituitary tuberculoma. (36/91)

Magnetic resonance spectroscopy (MRS) is a new, noninvasive method of diagnosing a lesion in cases where magnetic resonance (MR) imaging cannot reliably differentiate between two or more possible aetiologies. This case report describes a 20-year-old pregnant woman who developed sudden onset of left-sided hemiparesis. MR imaging of the brain revealed an infarct of the right middle cerebral artery and a suprasellar mass. The endocrine workup was normal. As she was 20 weeks pregnant, the option of a transsphenoidal biopsy of the pituitary lesion was rejected in favour of MRS . It demonstrated features characteristic of a tuberculoma. She showed marked clinical improvement after she was started on anti-tuberculous drugs. MRS is a rapidly-developing diagnostic modality, and may be a useful and safe option for investigating intracranial lesions in patients who cannot undergo invasive procedures.  (+info)

Multinucleate giant cells release functionally unopposed matrix metalloproteinase-9 in vitro and in vivo. (37/91)

Multinucleated giant cells (MGCs) are characteristic of granulomatous inflammation. Matrix metalloproteinase (MMP)-9, the major monocyte-derived matrix metalloproteinase, is key in inflammatory tissue damage. At 72 h, MGCs secrete 153 +/- 2.5 ng/mL MMP-9, compared with 115 +/- 3.8 ng/mL during macrophage differentiation (P<.05). In contrast, the level of MGC secretion-specific tissue inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1, is lower (P<.05). Mature MGCs secrete constitutively greater concentrations of MMP-9 than do monocytes or macrophages (P<.05). MGCs in tuberculous lymph-node biopsy samples express high MMP-9 levels adjacent to areas of necrosis, whereas TIMP-1 is not detected. Thus, MGCs are potentially important sources of MMP-9 secretion and may contribute to inflammatory tissue damage in human tuberculosis.  (+info)

Ferucarbotran versus Gd-DTPA-enhanced MR imaging in the detection of focal hepatic lesions. (38/91)

AIM: To evaluate the efficacy of ferucarbotran-enhanced MR imaging in the detection of focal hepatic lesions compared to plain and Gd-DTPA-enhanced MR imaging. METHODS: Fifty-nine patients with suspected focal hepatic lesions were admitted to the study. Plain MR imaging (FSE T(2)WI with fat suppression and GRE T(1)WI sequences) and Gd-DTPA dynamic enhanced MR of the liver were initially performed followed by ferucarbotran-enhanced MR imaging 48 h later (including GRE T(1)WI, FSE T(2)WI with fat suppression, and GRE T(2)WI sequences). Images were reviewed independently by three observers. Results were correlated with surgery and pathologic examination or reference examination, and sensitivity was statistically calculated for the different MR imaging sequences. RESULTS: Among all confirmed lesions (n = 133), ferucarbotran-enhanced MR imaging revealed 130 lesions on FSE T(2)WI with fat suppression, 115 lesions on dynamic T(1)WI GRE, and 127 lesions on GRE T(2)WI. Pre-contrast MR imaging revealed only 84 lesions on GRE T(1)WI and 106 lesions on FSE T(2)WI with fat suppression, while Gd-DTPA dynamic enhanced GRE T(1)WI revealed 123 lesions. For 44 micro-lesions (< 1.0 cm) in all patients the detection rates were as follows: ferucarbotran-enhanced FSE T(2)WI with fat suppression, 93.2% (41/44); ferucarbotran-enhanced GRE T(2)WI, 88.6% (39/44); Gd-DTPA dynamic-enhanced GRE T(1)WI, 79.5% (35/44); pre-contrast FSE T(2)WI with fat suppression, 54.5% (24/44); and pre-contrast GRE T(1)WI, 34.1% (15/44). In detecting micro-lesions, statistically significant difference was found for Ferucarbotran-enhanced FSE T(2)WI with fat suppression and GRE T(2)WI sequences compared to the other sequences (P < 0.05). CONCLUSION: Ferucarbotran-enhanced FSE T(2)WI with fat suppression and GRE T(2)WI sequences are superior in detecting micro-lesions (< 1 cm) in comparison with plain and Gd-DTPA dynamic-enhanced MR imaging.  (+info)

Usefulness of contrast-enhanced magnetic resonance imaging for evaluating solitary pulmonary nodules. (39/91)

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Intradural extramedullary tuberculoma of the thoracic spine: paradoxical response to antituberculous therapy. (40/91)

Intradural extramedullary tuberculoma of the spinal cord (IETSC) is a rare complication of tuberculosis, which can occur as a paradoxical response to antituberculous therapy. A 46-year-old woman with tuberculosis meningitis developed an acute sensory disturbance and paraplegia eight weeks after the antituberculous treatment was started. MRI revealed a cystic lesion at the Th 2 and 3 vertebrae levels, and continuous dural thickening. Laminectomy was performed; soft granulomas were unexpectedly observed inside the dura matter. After the operation, the patient experienced progressive improvement in motor strength. IETSC should be known as rare but possible complication of tuberculous meningitis.  (+info)