The presence of interleukin-13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis.
OBJECTIVE
To study the production of interleukin-13 (IL-13) in rheumatoid synovium and the effects of recombinant IL-13 on the phenotype and function of synovial fluid (SF) macrophages and T cells derived from patients with rheumatoid arthritis (RA).


METHODS
The presence of IL-13 in SF was studied using an IL-13-specific enzyme-linked immunosorbent assay (ELISA); the production of IL-13 was studied in SF mononuclear cells (SFMC) by reverse transcriptase-polymerase chain reaction. The effects of recombinant IL-13 on cytokine production by and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry, respectively. The effect of IL-13 on the proliferation of SFMC was determined by 3H-thymidine incorporation. The production and the effects of IL-13 were compared with those of IL-4.


RESULTS
IL-13 was present in 27 of 28 SF samples, and IL-13 messenger RNA (mRNA) was detectable in SFMC. Importantly, IL-13 levels were significantly higher than those of IL-4, and IL-13 protein and mRNA were expressed in several samples, although IL-4 synthesis was undetectable. Recombinant IL-13 significantly reduced the production of IL-1 beta and tumor necrosis factor alpha and the expression of CD16 and CD64 by SF macrophages, whereas the expression of HLA-DR and CD23 was increased. These effects on SF macrophages were similar to those observed with IL-4, but in contrast to IL-4, IL-13 had no growth-promoting effect on SF T cells.


CONCLUSIONS
IL-13 is consistently present in rheumatoid synovium. The ability of exogenous IL-13 to decrease the production of proinflammatory cytokines by SFMC suggests that it may have therapeutic potential in the treatment of patients with RA.
Isomäki
P
P
Turku Immunology Centre, Finland.
Luukkainen
R
R
Toivanen
P
P
Punnonen
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000032:analysis* / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D007596:Joints / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000166:cytology* / Q000276:immunology*; D013583:Synovial Membrane / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D007375:Interleukin-1; D018793:Interleukin-13; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4