Important immunoregulatory role of interleukin-11 in the inflammatory process in rheumatoid arthritis.
OBJECTIVE
To investigate the possible immunoregulatory role of interleukin-11 (IL-11) in rheumatoid arthritis (RA).


METHODS
IL-11 protein was assayed in RA tissue, and the effect of exogenous IL-11 on neutralization of endogenous IL-11 was investigated with respect to tumor necrosis factor alpha (TNFalpha), matrix metalloproteinase (MMP), and tissue inhibitor of metalloproteinases (TIMP) production.


RESULTS
IL-11 was found in RA synovial membranes, synovial fluids, and blood sera. Blockade of endogenous IL-11 resulted in a 2-fold increase in TNFalpha levels, which increased to 22-fold if endogenous IL-10 was also blocked. Addition of exogenous IL-11 inhibited spontaneous TNFalpha production in RA synovium only in the presence of soluble IL-11 receptor. However, exogenous IL-11 directly inhibited spontaneous MMP-1 and MMP-3 production, and up-regulated TIMP-1 in RA synovial tissue.


CONCLUSIONS
IL-11 has important endogenous immunoregulatory effects in RA synovium, which suggests that exogenous IL-11 may have therapeutic activity in RA.
The Mathilda and Terence Kennedy Institute of Rheumatology, London, UK.
J A
JA
Hermann
M A
MA
Hall
R N
RN
Maini
M
M
Feldmann
F M
FM
Brennan
D000276:Adjuvants, Immunologic / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000502:physiology; D017370:Interleukin-11 / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000378:metabolism; D018123:Receptors, Interleukin / Q000502:physiology; D011994:Recombinant Proteins; D012995:Solubility; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D007375:Interleukin-1; D017370:Interleukin-11; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008666:Metalloendopeptidases