Complete prevention of the clinical expression of adjuvant-induced arthritis in rats by cyclosporin-A and lobenzarit: the regulation of lymph node cell populations and cytokine production.
A single dose of either cyclosporin-A (CsA) or lobenzarit (CCA) given with an arthrogenic adjuvant completely prevented expression of experimental adjuvant arthritis in rats. The aim of this study was to understand how these drugs prevented the arthritis expression by studying the popliteal lymph nodes draining the arthritic joints at various times after adjuvant injection. Neither drug affected the proliferation in popliteal lymph nodes at the time arthritis was normally expressed, however, there was a marked change in the types of cells present. Immunofluorescence assays showed a reduction in the proportion of CD4+ cells, while the proportion of B-lymphocytes was almost doubled. This coincided with a marked elevation in the ability of these cells to produce interleukin (IL)-6. At the same time production of other cytokines (IL-2, tumour necrosis factor (TNF) and interferon (IFN)-gamma) was not greatly affected. However, one day after adjuvant injection IL-2 and IFN-gamma production was reduced. In vitro experiments showed that IL-6 production by lymphoid cells was relatively unaffected by CsA and CCA but IL-2, TNF and IFN-gamma were suppressed by CsA. The results indicate that CsA and CCA may modify the response to the arthritic adjuvant by specifically inhibiting IL-2, TNF and IFN-gamma production at the time of adjuvant injection. The lack of inhibition of IL-6 by these drugs reveals it may not play a key role in the initiation of this model of chronic inflammation.
Haynes
D R
DR
Department of Pathology, University of Adelaide, Australia.
Gadd
S J
SJ
Whitehouse
M W
MW
Mayrhofer
G
G
Vernon-Roberts
B
B
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D015704:CD4 Antigens / Q000187:drug effects; D002100:Cachexia / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
D018501:Antirheumatic Agents; D015704:CD4 Antigens; D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D062367:ortho-Aminobenzoates; D007371:Interferon-gamma; D016572:Cyclosporine; C015735:lobenzarit; D015232:Dinoprostone