Effects of pyrrolidine dithiocarbamate, an NF-kappaB inhibitor, on cytokine expression and ocular inflammation in experimental autoimmune anterior uveitis.
OBJECTIVE
The aim of this study was to investigate the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor (NF)-kappaB inhibitor, on cytokine expression and suppression of anterior chamber inflammation in experimental autoimmune anterior uveitis. Uveitis was induced in the Lewis rats with the injection of a melanin-associated antigen into the peritoneum and footpad. At defined time points, cytokine mRNA expressions in the iris and ciliary body were measured by using a semiquantitative polymerase chain-reaction method.


RESULTS
We found that interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF)-alpha mRNA expression peaked during the active phase of uveitis, whereas interleukin (IL)-10 mRNA increased during the disease resolution. In a separate experiment, PDTC (100 and 200 mg/kg/day) was administrated intraperitoneally daily after immunization. We found that PDTC (100 and 200 mg/kg/day) effectively suppressed ocular inflammation, as indicated by reduced clinical scores and inflammatory cells infiltration in aqueous humor and the iris and ciliary body.


CONCLUSIONS
The inhibitory effects of PDTC are mainly resulted from inhibiting the expression of proinflammatory cytokines, TNF-alpha and IFN-gamma but augmenting anti-inflammatory cytokines, IL-10 expression. These findings suggest that the application of NF-kappaB inhibitors may be a potential therapeutic method for the treatment of acute anterior uveitis.
Fang
I-Mo
IM
Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
Yang
Chang-Hao
CH
Lin
Chang-Pin
CP
Yang
Chung-May
CM
Chen
Muh-Shy
MS
D000818:Animals; D001082:Aqueous Humor / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002924:Ciliary Body / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D007498:Iris / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013859:Thiocarbamates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014606:Uveitis, Anterior / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid