PMID- 15958260
OWN - NLM
STAT- MEDLINE
DCOM- 20051024
LR  - 20090422
IS  - 1472-9792 (Print)
IS  - 1472-9792 (Linking)
VI  - 85
IP  - 4
DP  - 2005 Jul
TI  - Evaluating the role of tumor necrosis factor-alpha in experimental pulmonary 
      tuberculosis in the guinea pig.
PG  - 245-58
AB  - Tumor necrosis factor-alpha (TNF-alpha) is suggested to play multiple roles in 
      immune and pathologic responses in tuberculosis. In this study, we have developed 
      a system for the expression of recombinant guinea pig TNF-alpha (rgpTNF-alpha). 
      Using rgpTNF-alpha along with neutralizing anti-rgpTNF-alpha antiserum, we tested 
      the effect of modulating the levels of TNF-alpha on antigen-specific T cell 
      proliferation in splenocytes. By neutralizing TNF-alpha in the supernatant of 
      PPD-pulsed splenocytes with anti-rgpTNF-alpha, we observed hyperproliferation. 
      Conversely, the addition of rgpTNF-alpha resulted in a significant suppression of 
      PPD-induced lymphoproliferation. In addition, when unvaccinated and 
      BCG-vaccinated guinea pigs were treated with polyclonal rgpTNF-alpha antiserum 
      throughout the first 3 weeks following low-dose, pulmonary infection with 
      Mycobacterium tuberculosis H37Rv, we observed splenomegaly in BCG-vaccinated 
      guinea pigs. We also detected higher levels of splenic granuloma organization in 
      the non-vaccinated group as well as a significant number of plasma cells 
      associated with granulomata from the BCG-vaccinated group. These results suggest 
      that modulating the availability of TNF-alpha in BCG-vaccinated guinea pigs can 
      lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of 
      humoral immunity. Conversely, abrogating TNF-alpha activity in the context of a 
      hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue 
      them from immunopathological consequences of overproducing TNF-alpha.
FAU - Lasco, Todd M
AU  - Lasco TM
AD  - Department of Medical Microbiology and Immunology, The Texas A&M University 
      System-Health Science Center, College Station, TX 77843-1114, USA. 
      tlasco@mycoresearch.com
FAU - Cassone, Lynne
AU  - Cassone L
FAU - Kamohara, Hidenobu
AU  - Kamohara H
FAU - Yoshimura, Teizo
AU  - Yoshimura T
FAU - McMurray, David N
AU  - McMurray DN
LA  - eng
GR  - R01 AI-15495/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050303
PL  - Scotland
TA  - Tuberculosis (Edinb)
JT  - Tuberculosis (Edinburgh, Scotland)
JID - 100971555
RN  - 0 (BCG Vaccine)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibody Formation
MH  - BCG Vaccine/immunology
MH  - Base Sequence
MH  - Blotting, Western
MH  - Granuloma/immunology/microbiology
MH  - Guinea Pigs
MH  - Lymphocyte Activation
MH  - Mycobacterium bovis/*immunology
MH  - Splenomegaly/immunology/microbiology
MH  - T-Lymphocytes/*immunology
MH  - Tuberculosis, Pulmonary/*immunology/microbiology
MH  - Tumor Necrosis Factor-alpha/genetics/*physiology
EDAT- 2005/06/17 09:00
MHDA- 2005/10/26 09:00
CRDT- 2005/06/17 09:00
PHST- 2005/01/28 00:00 [accepted]
PHST- 2005/06/17 09:00 [pubmed]
PHST- 2005/10/26 09:00 [medline]
PHST- 2005/06/17 09:00 [entrez]
AID - S1472-9792(05)00015-6 [pii]
AID - 10.1016/j.tube.2005.01.001 [doi]
PST - ppublish
SO  - Tuberculosis (Edinb). 2005 Jul;85(4):245-58. doi: 10.1016/j.tube.2005.01.001. 
      Epub 2005 Mar 3.