PT - JOURNAL ARTICLE AU - Bengt Särnstrand AU - Anne-Helene Jansson AU - Giedre Matuseviciene AU - Annika Scheynius AU - Stefan Pierrou AU - Håkan Bergstrand TI - <em>N</em>,<em>N</em>′-Diacetyl-<span class="sc">l</span>-cystine—the Disulfide Dimer of <em>N</em>-acetylcysteine—Is a Potent Modulator of Contact Sensitivity/Delayed Type Hypersensitivity Reactions in Rodents DP - 1999 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1174--1184 VI - 288 IP - 3 4099 - http://jpet.aspetjournals.org/content/288/3/1174.short 4100 - http://jpet.aspetjournals.org/content/288/3/1174.full SO - J Pharmacol Exp Ther1999 Mar 01; 288 AB - 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 μmol/kg DiNAC leads toenhancement 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 treatmentaugments 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. The American Society for Pharmacology and Experimental Therapeutics