Regulation of serum chemokines following infliximab therapy in patients with rheumatoid arthritis.
OBJECTIVE
We studied the effects of the multiple infusions of infliximab, a chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody, on the serum chemokines levels in patients with active rheumatoid arthritis (RA).


METHODS
RA patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter with the same dose. All patients continued treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at weeks 0, 2, 6, 14, 38, prior to infusion, and additionally at week 62.


RESULTS
Initial infusion of infliximab caused reduction in serum IL-8, RANTES and MCP-1 (in all cases p < 0.001) levels. Subsequent infliximab administrations also significantly decreased serum chemokines levels, but was less effective. Prior to the first infliximab infusion serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) or CRP levels, number of swollen joints and disease activity score (DAS). Following next drug infusions such associations were far less significant. Infliximab treatment induced a significant reduction in the number of monocytes observed through the whole study (in all cases p < 0.05).


CONCLUSIONS
Anti-TNF-alpha antibody therapy accompanied by MTX, beside a rapid clinical improvement, reduced serum chemokines concentrations in RA patients. Subsequent administrations of infliximab sustained chemokines decrease, although to a lesser extent than the first two dose of infliximab.
Klimiuk
P A
PA
Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland. klimp@amb.edu.pl
Sierakowski
S
S
Domyslawska
I
I
Chwiecko
J
J
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood*; D018946:Chemokine CCL5 / Q000097:blood*; D006801:Humans; D000069285:Infliximab; D016209:Interleukin-8 / Q000097:blood*; D007596:Joints / Q000503:physiopathology; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016209:Interleukin-8; D002097:C-Reactive Protein; D000069285:Infliximab