Alteration of spleen lymphocyte populations in rats with arthritis induced by muramyl dipeptide analogue or complete adjuvant.
To examine the involvement of lymphocytes in the development of MDP-Lys(L18)-induced arthritis (MIA) in rats and the exacerbation of MIA by cyclosporin A (CsA), we analysed the spleen lymphocyte subset using monoclonal antibodies and flow cytometry during the development of arthritis and compared the results with those found in adjuvant-induced arthritis (AIA). Subcutaneous injection of MDP-Lys(L18) 4 mg/kg to male Lewis rats for 14 days caused very slight and quite clear increases in tarsal joint thickness on days 8 and 15, respectively. This increase was significantly enhanced by co-administration of CsA 10 mg/kg on both of these days. Adjuvant intracutaneously injected once increased the thickness only on day 15, and this was completely inhibited by CsA. The populations of CD4+ and CD8+ cells were increased and decreased, respectively, increasing the CD4+/CD8+ ratio, from day 8 in MIA. CsA enhanced the MDP-Lys(L18)-induced changes in these populations and caused additional decreases in the number of CD5+ cells. Only the CD4+ cell population was increased on day 15 in AIA, and this increase was inhibited by CsA. These results suggest that the spleen lymphocyte subsets in MIA have a different role from those in AIA, and that the contribution of enhancement of the subset changes to the exacerbating effect of CsA on MIA.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives; D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal; D001169:Arthritis, Experimental / Q000473:pathology*; D016516:CD4-CD8 Ratio; D016572:Cyclosporine / Q000633:toxicity*; D005434:Flow Cytometry; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D013643:Tarsus, Animal / Q000473:pathology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D016572:Cyclosporine; C036866:romurtide