PMID- 15212820
OWN - NLM
STAT- MEDLINE
DCOM- 20040803
LR  - 20040623
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 200
IP  - 2-3
DP  - 2004 Aug 5
TI  - Cytokine release does not improve the sensitivity and specificity of the direct 
      popliteal lymph node assay.
PG  - 247-54
AB  - The popliteal lymph node assay (PLNA) is being considered as a tool to predict 
      the potential of drugs for inducing systemic autoimmune and hypersensitivity 
      reactions. Despite the use of different technical approaches and the evaluation 
      of over 130 compounds, the sensitivity and specificity of the PLNA are still 
      debatable due to many false positive and negative responses. In this study, 
      cytokine production was assessed as a possible endpoint to improve the direct 
      (primary) PLNA. Diclofenac, imipramine, hydralazine, glafenin and minocycline 
      were tested using the classical procedure. TH1 cytokines (IL-2 and IFN-gamma), 
      TH2 cytokines (IL-4 and IL-5) and pro-inflammatory cytokines (IL-6, TNF-alpha, 
      monocyte chemoattractant protein-1 (MCP-1), IL-12p70 and IL-10) were measured in 
      the serum and in suspensions of popliteal lymph node cells of female Balb/c mice 
      by flow cytometry 7 days after drug administration. Only diclofenac and 
      imipramine induced a cellularity index above 5 (considered as a positive 
      response). Of the five tested drugs, only diclofenac induced a slight increase in 
      TH1 cytokines, but there were no effects on TH2 cytokine production whatever the 
      drug tested. Diclofenac increased the production of pro-inflammatory cytokines, 
      whereas the production of MCP-1 was increased by minocycline and decreased by 
      imipramine. No changes in serum cytokine levels were evident. These results 
      suggest that measuring cytokine release is unlikely to improve the sensitivity 
      and specificity of the direct PLNA.
FAU - Ravel, Guillaume
AU  - Ravel G
AD  - MDS Pharma Services, Les Oncins, 69210 St. Germain sur L'Arbresle, France. 
      guillaume.ravel@mdsps.com
FAU - Christ, Marielle
AU  - Christ M
FAU - Horand, Francoise
AU  - Horand F
FAU - Descotes, Jacques
AU  - Descotes J
LA  - eng
PT  - Journal Article
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Animals
MH  - Autoimmunity/*drug effects
MH  - Cells, Cultured
MH  - Cytokines/analysis/*metabolism
MH  - Drug Hypersensitivity/*pathology
MH  - Female
MH  - Flow Cytometry
MH  - Inflammation Mediators/analysis/metabolism
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Th1 Cells/drug effects/metabolism
MH  - Th2 Cells/drug effects/metabolism
EDAT- 2004/06/24 05:00
MHDA- 2004/08/04 05:00
CRDT- 2004/06/24 05:00
PHST- 2003/12/13 00:00 [received]
PHST- 2004/03/11 00:00 [accepted]
PHST- 2004/06/24 05:00 [pubmed]
PHST- 2004/08/04 05:00 [medline]
PHST- 2004/06/24 05:00 [entrez]
AID - S0300483X04001854 [pii]
AID - 10.1016/j.tox.2004.03.010 [doi]
PST - ppublish
SO  - Toxicology. 2004 Aug 5;200(2-3):247-54. doi: 10.1016/j.tox.2004.03.010.