Cytokine and chemokine receptor profile of peripheral blood mononuclear cells during treatment with infliximab in patients with active rheumatoid arthritis.
OBJECTIVE
To analyse immunological changes during treatment with a monoclonal anti-tumour necrosis factor alpha (TNFalpha) antibody, infliximab, in patients with rheumatoid arthritis (RA).


METHODS
25 patients with RA and 5 patients with other arthritides were studied during the first 6 weeks of treatment with infliximab. At the start of treatment and after 2 and 6 weeks, spontaneous expression of CCR3 and CCR5 on peripheral blood T cells and monocytes was studied by flow cytometry. The secretion and mRNA expression of interferon gamma (IFNgamma), interleukin (IL)4, IL5, and TNFalpha from phytohaemagglutinin (PHA) stimulated peripheral blood mononuclear cells was measured with an ELISA and RT-PCR. Plasma levels of C reactive protein, serum amyloid protein A, rheumatoid factor, and antibodies to filaggrin and citrullinated cyclic peptide were measured with an ELISA.


RESULTS
The number of CD4 T cells and CD14 monocytes expressing CCR3 (p = 0.013, p = 0.009, respectively) and CD8 T cells expressing CCR5 (p = 0.040) as well as PHA stimulated secretion of IL4 and IFNgamma (p<0.05) increased during treatment in patients with RA. 15 (60%) patients with RA achieved clinical response (at least ACR20) during the first 2 weeks. The number of T cells expressing CCR3 and CCR5 was higher before treatment in non-responders than in responders (p<0.05). The number of T cells increased in responders.


CONCLUSIONS
Increase in secretion of Th1 and Th2 cytokines together with induced expression of chemokine receptors on T cells and monocytes suggest restoration of peripheral cell mediated immunity and blockade of the accumulation of inflammatory cells in joints as response to treatment.
Nissinen
R
R
National Public Health Institute, Department of Molecular Medicine, Biomedicum, PO Box 104, 00251 Helsinki, Finland. riikka.nissinen@ktl.fi
Leirisalo-Repo
M
M
Peltomaa
R
R
Palosuo
T
T
Vaarala
O
O
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D000069285:Infliximab; D007381:Intermediate Filament Proteins / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000097:blood*; D019707:Receptors, Chemokine / Q000097:blood*; D012217:Rheumatoid Factor / Q000097:blood; D000685:Serum Amyloid A Protein / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001323:Autoantibodies; C515350:CCR3 protein, human; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D000069285:Infliximab