A 7-day oral treatment of patients with active rheumatoid arthritis using the prostacyclin analog iloprost: cytokine modulation, safety, and clinical effects.
OBJECTIVE
The purpose of this study was to investigate the plasma levels of tumor necrosis factor (TNF)-alpha, its soluble p55 and p75 receptors, ex vivo lipopolysaccharide (LPS)-stimulated TNF-alpha production, and plasma levels of interleukin 6, interleukin 1, and interleukin 10 during a 7-day oral administration of iloprost in patients with active rheumatoid arthritis.


METHODS
During oral 7-day administration of the prostacyclin analog iloprost, the plasma levels of TNF-alpha, soluble p55, and p75 TNF-alpha receptors, IL-1, IL-6, and IL-10 and C-reactive protein (CRP) in serum were determined on days -1, 1, 3, 4, 6, and 8 and after a treatment-free follow-up on day 15. In addition, the ex vivo TNF-alpha production in whole blood under LPS-stimulated and -unstimulated conditions were measured. Fifteen patients with active rheumatoid arthritis and baseline TNF-alpha plasma levels of > or =2 pg/ml were included in independent groups receiving 50 microg, 100 microg, or 150 microg iloprost per day in addition to their conventional antirheumatic therapy. The respective dose was given once daily from days 1 to 3 and doubled from days 4 to 7. The tender and swollen joint count (28 joints) and the patients' assessments of pain severity and general feeling (10-cm visual analog scale) were performed on days -1, 4, and 8 (end of treatment) and after a 7-day follow-up.


RESULTS
The patients showed decreased TNF-alpha levels during iloprost administration. The decrease in the ex vivo LPS-stimulated TNF-alpha production and plasma levels of the p75 TNF receptor were found to be associated with a decrease in the number of tender joints. Additionally, IL-6 was downregulated.


CONCLUSIONS
A 7-day oral administration of iloprost resulted in a change of in vivo and ex vivo cellular cytokine production, with reductions in TNF-alpha and p75 TNF receptor plasma levels. These changes were associated with clinical improvements in active rheumatoid arthritis.
Gao
Ino K
IK
Rheumatology Practice, Dossenheimer Landstr. 100, 69121 Heidelberg, Germany. inogao@t-online.de
Scholz
Peter
P
Boehme
Michael W J
MW
Norden
Cornelia
C
Lemmel
Ernst-Martin
EM
D000284:Administration, Oral; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage / Q000627:therapeutic use*; D007378:Interleukins / Q000097:blood; D007596:Joints / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D007378:Interleukins; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016285:Iloprost