N,N '-diacetyl-L-cystine - the disulfide dimer of N-acetylcysteine - is a potent modulator of contact sensitivity delayed type hypersensitivity reactions in rodents
B. Sarnstrand et al., N,N '-diacetyl-L-cystine - the disulfide dimer of N-acetylcysteine - is a potent modulator of contact sensitivity delayed type hypersensitivity reactions in rodents, J PHARM EXP, 288(3), 1999, pp. 1174-1184
Citations number
40
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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 con
tact sensitivity (CS)/delayed type hypersensitivity (DTH) reactions in rode
nts. Oral treatment of BALB/c mice with 0.003 to 30 mu mol/kg DINAC leads t
o enhancement of a CS reaction to oxazolone; DiNAC is 100 to 1000 times mor
e potent than NAC in this respect, indicating that it does not act as a pro
drug of NAC. Structure-activity studies suggest that a stereochemically-def
ined disulfide element is needed for activity. The DiNAC-induced enhancemen
t of the GS reaction is counteracted by simultaneous NAG-treatment; in cont
rast, the CS reaction is even more enhanced in animals treated with DiNAC t
ogether with the glutathione-depleting agent buthionine sulfoximine. These
data suggest that DiNAC acts via redox processes. Immunohistochemically, ea
r specimens from oxazolone-sensitized and -challenged BALB/c mice treated w
ith DiNAC display increased numbers of CD8(+) cells. DiNAC treatment augmen
ts the CS reaction also when fluorescein isothiocyanate is used as a sensit
izer in BALB/c mice; this is a purported TH2 type of response. However, whe
n dinitrofluorobenzene is used as a sensitizer, inducing a purported TH1 ty
pe of response, DiNAC treatment reduces the reaction. Treatment with DiNAC
also reduces a DTH footpad-swelling reaction to methylated BSA. Collectivel
y, these data indicate that DiNAC in vivo acts as a potent and effective im
munomodulator that can either enhance or reduce the CS or DTH response depe
nding on the experimental conditions.