Effect of cytokine modulation by thalidomide on the granulomatous response in murine tuberculosis.
METHODS
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.


METHODS
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-alpha, interleukin 6 (IL-6) and IL-10 protein levels (blood) and mRNA expression (lungs). IL-12 and interferon-gamma 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.


CONCLUSIONS
Thalidomide immunomodulation reduces inflammatory cytokines and concomitant lung pathology following acute aerosol M. tuberculosis infection, without increasing the bacillary load.
Rockefeller University, New York, NY 10021, USA.
A L
AL
Moreira
L
L
Tsenova-Berkova
J
J
Wang
P
P
Laochumroonvorapong
S
S
Freeman
V H
VH
Freedman
G
G
Kaplan
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009336:Necrosis; D012333:RNA, Messenger / Q000378:metabolism; D018709:Statistics, Nonparametric; D013792:Thalidomide / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013792:Thalidomide