PMID- 9778221
OWN - NLM
STAT- MEDLINE
DCOM- 19981103
LR  - 20131121
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 41
IP  - 10
DP  - 1998 Oct
TI  - Therapeutic actions of cyclosporine and anti-tumor necrosis factor alpha in 
      collagen-induced arthritis and the effect of combination therapy.
PG  - 1806-12
AB  - OBJECTIVE: To define the mechanisms of action of 2 novel drugs, cyclosporine and 
      anti-tumor necrosis factor alpha (TNFalpha), in collagen-induced arthritis and to 
      determine the effect of combination therapy. METHODS: Type II collagen-immunized 
      DBA/1 mice with established arthritis were treated with cyclosporine alone, 
      anti-TNFalpha alone, cyclosporine plus anti-TNFalpha, or saline. RESULTS: 
      Cyclosporine was found to ameliorate arthritis, suppress interferon-gamma 
      (IFNgamma) production by CD4+ T cells, and reduce TNFalpha expression in 
      arthritic joints. However, cyclosporine did not directly inhibit TNFalpha 
      production by macrophages, indicating that the decrease in TNFalpha expression 
      observed in vivo was probably an indirect consequence of the reduction in type 1 
      T helper cell activity. Anti-TNFalpha also reduced IFNgamma production by T 
      cells, indicating that TNFalpha is involved in the cellular immune response to 
      collagen. Combined treatment with cyclosporine plus anti-TNFalpha had an additive 
      therapeutic effect. CONCLUSION: Although cyclosporine and anti-TNFalpha target 
      different points in the inflammatory pathway, there is an overlap in the 
      consequences of their actions in vivo.
FAU - Williams, R O
AU  - Williams RO
AD  - Kennedy Institute of Rheumatology, London, UK.
FAU - Mauri, C
AU  - Mauri C
FAU - Mason, L J
AU  - Mason LJ
FAU - Marinova-Mutafchieva, L
AU  - Marinova-Mutafchieva L
FAU - Ross, S E
AU  - Ross SE
FAU - Feldmann, M
AU  - Feldmann M
FAU - Maini, R N
AU  - Maini RN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Arthritis, Experimental/*drug therapy/immunology
MH  - Collagen/*immunology
MH  - Cyclosporine/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Male
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Th1 Cells/drug effects/immunology
MH  - Tumor Necrosis Factor-alpha/immunology
EDAT- 1998/10/20 00:00
MHDA- 1998/10/20 00:01
CRDT- 1998/10/20 00:00
PHST- 1998/10/20 00:00 [pubmed]
PHST- 1998/10/20 00:01 [medline]
PHST- 1998/10/20 00:00 [entrez]
AID - 10.1002/1529-0131(199810)41:10<1806::AID-ART12>3.0.CO;2-9 [doi]
PST - ppublish
SO  - Arthritis Rheum. 1998 Oct;41(10):1806-12. doi: 
      10.1002/1529-0131(199810)41:10<1806::AID-ART12>3.0.CO;2-9.