PMID- 7642306
OWN - NLM
STAT- MEDLINE
DCOM- 19950921
LR  - 20220316
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 63
IP  - 9
DP  - 1995 Sep
TI  - Effect of anti-tumor necrosis factor alpha antibodies on histopathology of 
      primary Salmonella infections.
PG  - 3674-82
AB  - We reported that administration of anti-tumor necrosis factor alpha 
      (anti-TNF-alpha) antibodies exacerbates the course of a Salmonella infection in 
      both susceptible and resistant mice by preventing the suppression of bacterial 
      growth in the reticuloendothelial system. In the present study, we evaluated the 
      effect of in vivo neutralization of TNF-alpha on the histopathology of primary 
      Salmonella infections. We show that in primary infections, the suppression of 
      bacterial growth in the reticuloendothelial system coincides with granuloma 
      formation in the spleen and liver. Administration of anti-TNF-alpha globulins on 
      day -1 of salmonellosis affected neither the histological picture nor the course 
      of the infection in the early stages of the disease (days 1 to 3), with splenic 
      and hepatic lesions consisting mainly of polymorphonuclear leukocytes (PMNs); 
      conversely, later in infection (days 3 to 7), the treatment inhibited the 
      formation of granulomas. When the anti-TNF-alpha treatment was started well after 
      the suppression of bacterial growth in the reticuloendothelial system and the 
      formation of granulomatous lesions in the spleen and liver, a prompt relapse of 
      the infection and regression of already established granulomas were seen. In 
      anti-TNF-alpha-treated mice, salmonellae were found inside macrophages and PMNs 
      and extracellularly in the necrotic tissue of the spleen, while in the liver the 
      organisms were seen mainly in inflammatory mononuclear cells, resident Kupffer 
      cells, and hepatocytes and occasionally in the extracellular compartment within 
      necrotic lesions. The bacteria appeared most often in clusters, being 
      morphologically intact when in the extracellular space or within hepatocytes, 
      while undergoing various degrees of degeneration when inside phagocytes. The 
      results suggest that TNF-alpha is required for granuloma formation in 
      salmonellosis and that its neutralization does not completely abrogate the 
      bactericidal activity of macrophages and PMNs. Salmonellae were observed to grow 
      within both hepatocytes and phagocytes but were killed only in the latter.
FAU - Mastroeni, P
AU  - Mastroeni P
AD  - Department of Microbiology, Medical School, University of Newcastle, Newcastle 
      upon Tyne, United Kingdom.
FAU - Skepper, J N
AU  - Skepper JN
FAU - Hormaeche, C E
AU  - Hormaeche CE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Immune Sera)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
EIN - Infect Immun 1995 Dec;63(12):4966
MH  - Animals
MH  - Female
MH  - Granuloma/pathology
MH  - Immune Sera/*immunology
MH  - Liver/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Salmonella Infections, Animal/*pathology
MH  - Salmonella typhimurium/isolation & purification
MH  - Spleen/pathology
MH  - Tumor Necrosis Factor-alpha/*physiology
PMC - PMC173509
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
PMCR- 1995/09/01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
PHST- 1995/09/01 00:00 [pmc-release]
AID - 10.1128/iai.63.9.3674-3682.1995 [doi]
PST - ppublish
SO  - Infect Immun. 1995 Sep;63(9):3674-82. doi: 10.1128/iai.63.9.3674-3682.1995.