The effect of ebselen on T-lymphocyte migration to arthritic joints and dermal inflammatory reactions in the rat.
We have previously observed that ebselen (PZ 51, 2-Phenyl-1,2-Bensoisoselenazol-3-(2H)-one) can inhibit human polymorphonuclear leukocyte (PMNL) transendothelial migration in vitro and PMNL migration to arthritic joints and dermal inflammatory reactions in rats. In this study, we investigated the effect of ebselen on T-lymphocyte migration to the inflamed joints in rats with adjuvant arthritis (AA) and to dermal inflammation induced by cytokines (IFN gamma, mTNF alpha), cytokine inducing stimuli (poly I:C and LPS), or a delayed type hypersensitivity (DTH) reaction. Treatment of rats with AA with ebselen (100 mg/kg/day) p.o. for three days significantly reduced accumulation of 111In-labelled spleen T-cells (SPLT) in the arthritic joints, including forepaws, carpal joints, hindpaws and talar joints, and in all the above dermal inflammatory reactions. The inhibitory effect of ebselen on SPLT cell accumulation was greater than with indomethacin (2 mg/kg/day) and was observed within 3 h of initiation of ebselen treatment. Ebselen also inhibited SPLT migration to mandibular, axillary and mesenteric lymph nodes, and to the spleen. The results suggest that not only does ebselen inhibit SPLT migration to inflamed joints and to dermal inflammation but it also may inhibit lymphocyte homing and recirculation. Whether these effects of ebselen are related to its reported inhibition of cellular activation and intracellular signalling requires further investigation. However, the inhibition of T-lymphocyte migration reported here and of PMNL migration reported previously may both be beneficial in the treatment of human arthritis.
Gao
J X
JX
Department of Pediatrics and Microbiology-Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Issekutz
A C
AC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000473:pathology*; D001393:Azoles / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000473:pathology*; D006968:Hypersensitivity, Delayed / Q000473:pathology; D007202:Indicators and Reagents; D007213:Indomethacin / Q000494:pharmacology; D007271:Injections, Intradermal; D054833:Isoindoles; D007596:Joints / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D016207:Cytokines; D007202:Indicators and Reagents; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D007213:Indomethacin