Decreased ex vivo production of TNF-alpha and IL-8 by peripheral blood cells of patients with rheumatoid arthritis after infliximab therapy.
Monoclonal antibody against TNF-alpha such as infliximab has shown clinical efficacy in controlling the inflammatory signs and symptoms of rheumatoid arthritis (RA), but the detailed immunotherapeutic mechanism is not fully understood. We investigated 19 patients with active RA who were treated with infliximab (3 mg/kg) at weeks 0, 2, 6 and 14. Peripheral blood was obtained from the patients at weeks 0 and 14 and cultured with mitogens phytohaemagglutinin (PHA) and lipopolysaccharide (LPS). The concentrations of cytokines and soluble adhesion molecules (sICAM-1, sICAM-3, sE-selectin, sP-selectin, sVCAM-1 and sPECAM-1) in supernatant fluids or plasma were measured by flow cytometry and ELISA. After infliximab treatment, the absolute and percentage increases in release of inflammatory cytokine TNF-alpha and potent neutrophil chemoattractant IL-8 upon PHA and LPS activation were significantly decreased when compared to those of before treatment (all P<0.01). The increased releases of IL-6, IL-1beta, IL-18 and IL-12 upon mitogen activation were similar before and after infliximab treatment (all P>0.05). Plasma concentrations of these cytokines and soluble adhesion molecules did not differ significantly before and after infliximab treatment. Our study suggests that the reduction in synovial inflammation may be due to the decreased production of TNF-alpha and IL-8, and hence the number of neutrophils and other pro-inflammatory leukocytes infiltrating into the inflamed sites.
Lun
S W M
SW
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Wong
C K
CK
Tam
L S
LS
Li
E K
EK
Lam
C W K
CW
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D000069285:Infliximab; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood
D000911:Antibodies, Monoclonal; D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008727:Methotrexate