• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.669-676
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• 1995

Background: The cell-mediated immunity is needed for eradicating the tubercle bacilli. Prostaglandin(PG), especially PG $E_2$, is involved in cellular immunosuppression. It is known that the PG $E_2$ is suppressed by indomethacin. For using indomethacin as a immunomodulator of intractable pulmonary tuberculosis(Tbc) patients, we measured the tuberculin skin test(TST) and the plasma PG $E_2$ levels. Method: The forty-eight inpatients with sputum positive acid-fast stain bacilli were classified into 6 groups according to antiTbc chemotherapy history(new and intractable cases), plain chest roetgenogram(minimal and far advanced cases), and TST reaction(nagative and positive cases). Except for one group(n=2; new, minimal, and negative cases of TST reaction) of the 6 groups, all subjects(n=46) were measured for the plasma PG $E_2$, levels with radioimmunoassay. Results: 1) There was no significant difference in the plasma PG $E_2$ levels among A group(far advanced and positive TST reaction cases, n=10, $11.22{\pm}2.86\;pg/ml$), B group(minimal and negative TST reaction cases, n=9, $11.35{\pm}2.20$) and C group(far advanced and positive TST reaction cases, n=7, $11.11{\pm}2.30$) in the new cases(p>0.05). 2) There was no significant difference in the plasma PG $E_2$ levels between positive(n=10, $9.25{\pm}2.21$) and negative(n=10, $8.25{\pm}1.13$) groups by TST in the intractable cases(p>0.05). 3) Comparing the plasma PG $E_2$ levels between new(n=26, $11.35{\pm}2.41$) and intractable(n=20, $8.75{\pm}1.78$) groups, the intractable group had significi- andy lower plasma PG $E_2$ levels(p<0.05). 4) There was no significant difference in the plasma PG $E_2$ levels between negative(n=19, $9.88{\pm}2.43$) and positive(n=27, $10.46{\pm}2.56$) groups by TST(p>0.05). 5) There was no significant difference in the plasma PG $E_2$ levels between male(n=32, $10.07{\pm}2.44$) and female(n=14, $10.56{\pm}2.70$)(p>0.05). 6) There was no significant difference in the plasma PG $E_2$ levels among 2nd(n=5, $10.21{\pm}2.86$), 3rd(n=9, $9.97{\pm}2.47$), 4th(n=13, $11.35{\pm}2.33$) and 5th(n=19, $9.57{\pm}2.48$) decades(p>0.05). 7) There was no significant correlation between the induration sizes of the TST and the plasma PG $E_2$ levels(r=0.054, p>0.05). Conclusion: From the above results, the plasma PG $E_2$ levels of intractable group are not higher as the authors had expected. There was no significant difference in the plasma PG $E_2$ levels by the lesion sizes of plain chest roentgenogram and the induration sizes of TST, so more study will be needed to use the indomethacin as a immunomodulator for intractable pulmonary tuberculosis patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.846-860
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• 1998

Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.