Anti-tumour necrosis factor (TNF) alpha treatment of rheumatoid arthritis (infliximab) selectively down regulates the production of interleukin (IL) 18 but not of IL12 and IL13.
OBJECTIVE
To measure interleukin (IL)18 serum concentrations in patients with rheumatoid arthritis (RA) undergoing infliximab treatment (tumour necrosis factor (TNF) alpha blockade) and to evaluate the concomitant modification of IL12 and IL13 serum concentrations, two cytokines belonging to the Th1 and Th2 profile respectively and biologically related to IL18.


METHODS
Ten patients with RA not responding to disease modifying antirheumatic drugs (DMARDs) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks. Serum samples were collected from all patients before each infusion and assayed for IL18, IL12, and IL13 by enzyme linked immunosorbent assay (ELISA); IL18 was also measured eight weeks after the last infusion.


RESULTS
Serum concentrations of IL18 in all patients were already markedly reduced from baseline after two weeks (p<0.005). Serum IL18 was also decreased in a stable manner after six (p<0.01) and 14 weeks (p<0.01) compared with baseline concentrations. No significant modifications were found in serum concentrations of IL12 and IL13 at any time point.


CONCLUSIONS
There was a rapid and persistent decrease in serum concentrations of IL18 in all the patients studied. This result provides evidence of an in vivo regulation of IL18 by TNFalpha and suggests that anti-TNFalpha therapy is likely to interrupt the synergistic effect between these two cytokines.
Dipartimento di Terapia Medica, Cattedra di Reumatologia, Università La Sapienza, Roma, Italy.
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V
Pittoni
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M
Bombardieri
F R
FR
Spinelli
R
R
Scrivo
C
C
Alessandri
F
F
Conti
A
A
Spadaro
G
G
Valesini
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D000069285:Infliximab; D018664:Interleukin-12 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D018793:Interleukin-13; D020382:Interleukin-18; D018664:Interleukin-12; D000069285:Infliximab