Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-4-1
pubmed:abstractText
Oral N-acetyl-L-cysteine (NAC) is used clinically for treatment of chronic obstructive pulmonary disease. NAC is easily oxidized to its disulfide. We show here that N,N'-diacetyl-L-cystine (DiNAC) is a potent modulator of contact sensitivity (CS)/delayed type hypersensitivity (DTH) reactions in rodents. Oral treatment of BALB/c mice with 0.003 to 30 micromol/kg DiNAC leads to enhancement of a CS reaction to oxazolone; DiNAC is 100 to 1000 times more potent than NAC in this respect, indicating that it does not act as a prodrug of NAC. Structure-activity studies suggest that a stereochemically-defined disulfide element is needed for activity. The DiNAC-induced enhancement of the CS reaction is counteracted by simultaneous NAC-treatment; in contrast, the CS reaction is even more enhanced in animals treated with DiNAC together with the glutathione-depleting agent buthionine sulfoximine. These data suggest that DiNAC acts via redox processes. Immunohistochemically, ear specimens from oxazolone-sensitized and -challenged BALB/c mice treated with DiNAC display increased numbers of CD8(+) cells. DiNAC treatment augments the CS reaction also when fluorescein isothiocyanate is used as a sensitizer in BALB/c mice; this is a purported TH2 type of response. However, when dinitrofluorobenzene is used as a sensitizer, inducing a purported TH1 type of response, DiNAC treatment reduces the reaction. Treatment with DiNAC also reduces a DTH footpad-swelling reaction to methylated BSA. Collectively, these data indicate that DiNAC in vivo acts as a potent and effective immunomodulator that can either enhance or reduce the CS or DTH response depending on the experimental conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1174-84
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10027856-Acetylcysteine, pubmed-meshheading:10027856-Adjuvants, Immunologic, pubmed-meshheading:10027856-Animals, pubmed-meshheading:10027856-CD8-Positive T-Lymphocytes, pubmed-meshheading:10027856-Cystine, pubmed-meshheading:10027856-Dermatitis, Contact, pubmed-meshheading:10027856-Dinitrofluorobenzene, pubmed-meshheading:10027856-Ear, pubmed-meshheading:10027856-Female, pubmed-meshheading:10027856-Fluorescein-5-isothiocyanate, pubmed-meshheading:10027856-Foot, pubmed-meshheading:10027856-Granuloma, pubmed-meshheading:10027856-Hypersensitivity, Delayed, pubmed-meshheading:10027856-Immunohistochemistry, pubmed-meshheading:10027856-Lymphocyte Count, pubmed-meshheading:10027856-Male, pubmed-meshheading:10027856-Mice, pubmed-meshheading:10027856-Mice, Inbred BALB C, pubmed-meshheading:10027856-Mice, Inbred Strains, pubmed-meshheading:10027856-Oxazolone, pubmed-meshheading:10027856-Rabbits, pubmed-meshheading:10027856-Serum Albumin, Bovine
pubmed:year
1999
pubmed:articleTitle
N,N'-Diacetyl-L-cystine-the disulfide dimer of N-acetylcysteine-is a potent modulator of contact sensitivity/delayed type hypersensitivity reactions in rodents.
pubmed:affiliation
Department of Pharmacology, Astra Draco AB, Lund, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't