TY - JOUR
T1 - Effect of cytokine modulation by thalidomide on the granulomatous response in murine tuberculosis
AU - Moreira, A. L.
AU - Tsenova-Berkova, L.
AU - Wang, J.
AU - Laochumroonvorapong, P.
AU - Freeman, S.
AU - Freedman, V. H.
AU - Kaplan, G.
N1 - Funding Information:
We would like to thank Marguerite Nulty for secretarial help, Judy Adams for helping to prepare the figures, Dr Patrick Haslett for critical and helpful discussions during the preparation of this manuscript, and Dr John Belisle for preparing the stocks of M. tuberculosis under the NIH contract NO 1-A_I-5147 . The assistance of Dr Angelo Izzo, Dr Pamela Dunn, Rom LaCourse, Linda Schaefer and Debra Duso of the Trudeau Institute is greatly appreciated. This work was supported in part by US Public Health Service grant AI 33124 and by Celgene Corporation (Warren, NJ). Andr6 Luis Moreira is a Villares Fellow.
PY - 1997
Y1 - 1997
N2 - Setting: Experimental murine tuberculosis. Objective: To evaluate the effect of cytokine modulation by thalidomide on the progression of the lung granulomatous response following aerosol tuberculosis infection in mice. Design: Mice infected by the respiratory route with 200-500 viable Mycobacterium tuberculosis Erdman were treated with daily subcutaneous injections of thalidomide (30 mg/kg) or saline for 4 weeks. The bacillary load, granulomatous response and cytokine production in the lungs were evaluated. Results: Aerosol M. tuberculosis infection resulted in a progressive granulomatous response in the lungs. At 28 days after infection, large granulomata with central necrosis and no apoptosis were observed. The infection induced high serum and lung cytokine mRNA levels. Thalidomide treatment resulted in a significant reduction in tumor necrosis factor-α, interleukin 6 (IL-6) and IL-10 protein levels (blood) and mRNA expression (lungs). IL-12 and interferon-γ were unaffected. The lungs of thalidomide-treated mice had smaller granulomata with apoptotic cells and no necrosis. Thalidomide treatment did not change the bacillary load. Conclusion: Thalidomide immunomodulation reduces inflammatory cytokines and concomitant lung pathology following acute aerosol M. tuberculosis infection, without increasing the bacillary load.
AB - Setting: Experimental murine tuberculosis. Objective: To evaluate the effect of cytokine modulation by thalidomide on the progression of the lung granulomatous response following aerosol tuberculosis infection in mice. Design: Mice infected by the respiratory route with 200-500 viable Mycobacterium tuberculosis Erdman were treated with daily subcutaneous injections of thalidomide (30 mg/kg) or saline for 4 weeks. The bacillary load, granulomatous response and cytokine production in the lungs were evaluated. Results: Aerosol M. tuberculosis infection resulted in a progressive granulomatous response in the lungs. At 28 days after infection, large granulomata with central necrosis and no apoptosis were observed. The infection induced high serum and lung cytokine mRNA levels. Thalidomide treatment resulted in a significant reduction in tumor necrosis factor-α, interleukin 6 (IL-6) and IL-10 protein levels (blood) and mRNA expression (lungs). IL-12 and interferon-γ were unaffected. The lungs of thalidomide-treated mice had smaller granulomata with apoptotic cells and no necrosis. Thalidomide treatment did not change the bacillary load. Conclusion: Thalidomide immunomodulation reduces inflammatory cytokines and concomitant lung pathology following acute aerosol M. tuberculosis infection, without increasing the bacillary load.
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U2 - 10.1016/S0962-8479(97)90015-0
DO - 10.1016/S0962-8479(97)90015-0
M3 - Article
C2 - 9666962
AN - SCOPUS:0031444981
SN - 0962-8479
VL - 78
SP - 47
EP - 55
JO - Tubercle and Lung Disease
JF - Tubercle and Lung Disease
IS - 1
ER -
