PMID- 9570330
OWN - NLM
STAT- MEDLINE
DCOM- 19980513
LR  - 20190819
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 125
IP  - 2-3
DP  - 1998 Feb 6
TI  - A modified murine local lymph node assay for the differentiation of contact 
      photoallergy from phototoxicity by analysis of cytokine expression in 
      skin-draining lymph node cells.
PG  - 149-68
AB  - Since predictive differentiation of photoallergenic from phototoxic reactions, 
      induced by low molecular weight compounds, represents a current problem, we tried 
      to improve the differentiation between the two reactions by using a modified 
      protocol of the local lymph node assay (LLNA). Briefly, groups of female BALB/c 
      mice received compound solution or vehicle alone on the dorsum of both ears on 3 
      consecutive days. Immediately after compound application indicated groups of mice 
      were exposed to a UVA light-dose of 10 J/cm2. Auricular lymph nodes draining the 
      ear tissue were excised 24 h following the last exposure. Evaluation consisted of 
      assessing lymph node weights and cell counts to monitor organ hyperplasia and in 
      vivo-proliferative events following substance application. Furthermore, we 
      analysed cytokine gene transcription in freshly prepared lymph node cells (LNC) 
      and the cytokine release in vitro by restimulated CD4+ T-cells and antigen 
      presenting cells (APC), both purified from the skin-draining lymph nodes. Both 
      contact (photo) allergenic (oxazolone and tetrachlorosalicylanilide) and 
      phototoxic substances (8-methoxypsoralen and acridine) caused a dose dependent 
      increase in lymph node weights and cell counts pointing to an inflammatory 
      process in the lymph nodes. Analysis of cytokine gene transcription ex vivo and 
      cytokine release in vitro revealed that during the induction phase of contact 
      (photo) allergy CD4+ T-cells produced IL-2 and IFN-gamma as well as IL-4 and 
      IL-10, whereas IL-6 was derived from APC. In contrast, phototoxic reactions 
      caused only an upregulation of IL-2 and IFN-gamma. Furthermore, we demonstrate 
      that the release of IL-4 and IL-10 by CD4+ T-cells was clearly increased, whereas 
      IL-6 and IFN-gamma expression was reduced or not changed following a challenge 
      with contact (photo) allergens revealing an allergy-indicative shift in cytokine 
      expression. In conclusion, our results show that contact photoallergenic 
      reactions could be differentiated from phototoxic events by analysis of LNC 
      cytokine expression patterns.
FAU - Ulrich, P
AU  - Ulrich P
AD  - Experimental Toxicology, Novartis Pharma AG, Basel, Switzerland. 
      peter.ulrich@pharma.novartis.com
FAU - Homey, B
AU  - Homey B
FAU - Vohr, H W
AU  - Vohr HW
LA  - eng
PT  - Journal Article
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Cytokines)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*radiation effects
MH  - Cytokines/*biosynthesis/genetics
MH  - Dermatitis, Photoallergic/*diagnosis/metabolism
MH  - Dermatitis, Phototoxic/*diagnosis/metabolism
MH  - Diagnosis, Differential
MH  - Drainage
MH  - Female
MH  - Hyperplasia/pathology
MH  - Interleukin-10/biosynthesis
MH  - Interleukin-4/biosynthesis
MH  - Lymph Nodes/pathology/*radiation effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Skin/immunology
MH  - Transcription, Genetic
MH  - Ultraviolet Rays
MH  - Up-Regulation
EDAT- 1998/05/07 00:00
MHDA- 1998/05/07 00:01
CRDT- 1998/05/07 00:00
PHST- 1998/05/07 00:00 [pubmed]
PHST- 1998/05/07 00:01 [medline]
PHST- 1998/05/07 00:00 [entrez]
AID - S0300-483X(97)00156-X [pii]
AID - 10.1016/s0300-483x(97)00156-x [doi]
PST - ppublish
SO  - Toxicology. 1998 Feb 6;125(2-3):149-68. doi: 10.1016/s0300-483x(97)00156-x.