Combination therapy with cyclosporine and methotrexate in patients with early rheumatoid arthritis soon inhibits TNFalpha production without decreasing TNFalpha mRNA levels. An in vivo and in vitro study.
OBJECTIVE
To evaluate the ability of two different combination therapies with prednisone (PDN), methotrexate (MTX) and cyclosporine (CSA) to modulate both TNFalpha transcription and production in early rheumatoid arthritis (RA).


METHODS
24 patients with early RA received a step-down bridge therapy with MTX and PDN (group A). Twelve patients out of the 24 randomly received also CSA (group B). Blood samples and peripheral blood mononuclear cells (PBMC) were collected at different times. TNFalpha levels were measured both in sera and in PBMC supernatants. TNFalpha mRNA was assessed by use of RT-PCR.


RESULTS
10 patients in group A and 9 in group B improved. At baseline, RA patients serum TNFalpha levels were increased compared to controls (p < 0.001) and did not correlate with clinical and serological parameters. These levels decreased within the first month of therapy in both groups, the lower levels being observed in the sera of CSA treated patients. After 30 days of therapy, TNFalpha levels in group B supernatants were significantly lower than those observed in group A, both after 24 and 48 hours of PHA stimulation (p < 0.03 and p < 0.05 respectively). TNFalpha mRNA levels never differed between patients and controls, independently of both the clinical picture and the assigned therapy.


CONCLUSIONS
The addition of CSA to a treatment regimen of PDN + MTX lowers TNFalpha production in vitro without decreasing TNFalpha mRNA expression. This effect could help to induce early immunosoppressive and therapeutic effects during RA.
Giacomelli
R
R
Clinica Medica, University of L'Aquila, Italy. roberto.giacomelli@cc.univaq.it
Cipriani
P
P
Matucci Cerinic
M
M
Fulminis
A
A
Barattelli
G
G
Pingiotti
E
E
Di Franco
M
M
Trotta
A
A
Perricone
R
R
Zazzeroni
F
F
Alesse
E
E
Tonietti
G
G
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D018501:Antirheumatic Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D008727:Methotrexate