Selective activation of mast cells in rheumatoid synovial tissue results in production of TNF-alpha, IL-1beta and IL-1Ra.
OBJECTIVE
To study the consequences of mast cell activation in human synovial tissue.


METHODS
Synovial tissue was obtained from 18 RA patients and mast cells was selectively activated in synovial tissue explant cultures. Expression of TNF-alpha, IL-1beta and IL-1Ra were determined and tissue distribution of IL-1beta was studied.


RESULTS
Compared to untreated synovia, selective activation of synovial mast cells increased significantly the production of TNF-alpha (0.49 +/- 0.88 vs. 4.56 +/- 3.18 pg/mg wet tissue, p < 0.001) and IL-1beta (0.058 +/- 0.032 vs. 2.55 +/- 1.98 pg/mg wet tissue, p = 0.013). The expression of TNF-alpha and IL-1beta mRNA increased significantly (19-fold (p = 0.009) and 13-fold (p = 0.031), respectively). Mast cell activation induced IL-1beta expression in particular in nearby CD68 positive synovial macrophages. Secretion of IL-1Ra was also increased but to a lesser degree than that of IL-1beta.


CONCLUSIONS
Synovial mast cells produce proinflammmatory cytokines and may thus contribute to the inflammation in RA.
Sandler
C
C
Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Kasarmikatu 11-13, 00130 Helsinki, Finland.
Lindstedt
K A
KA
Joutsiniemi
S
S
Lappalainen
J
J
Juutilainen
T
T
Kolah
J
J
Kovanen
P T
PT
Eklund
K K
KK
D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D007717:Knee / Q000601:surgery; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008875:Middle Aged; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007073:Immunoglobulin E; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule