Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1β and inhibited by peroxisome proliferator activated receptor α agonist.
BACKGROUND
Infrapatellar fat pad (IPFP) might be involved in osteoarthritis (OA) by production of cytokines. It was hypothesised that production of cytokines is sensitive to environmental conditions.


OBJECTIVE
To evaluate cytokine production by IPFP in response to interleukin (IL)1β and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor α (PPARα), which is also activated by lipid-lowering drugs such as fibrates.


METHODS
Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (five donors) and synovium (six donors) were cultured with IL-1β and PPARα agonist Wy14643. Gene expression of IL-1β, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)α, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNFα, MCP1 and prostaglandin E(2) were compared with unstimulated IPFP and synovium explants.


RESULTS
IPFP released large amounts of inflammatory cytokines, adipokines and growth factors. IL-1β increased gene expression of PTGS2, TNFα, IL-1β, IL-6 and VEGF and increased TNFα release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE(2) release did not increase significantly. Synovium responded to IL-1β similarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1β, TNFα, MCP1, VEGF and leptin in IPFP explants and IL-1β, TNFα, IL-6, IL-10 and VEGF in synovium that responded to IL-1β.


CONCLUSIONS
IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1β and decreased by a PPARα agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating inflammatory properties of IPFP and synovium.
Department of Orthopaedic Surgery and Traumatology, University of Antwerp, Antwerp, Belgium. s.clockaerts@erasmusmc.nl
Stefan
S
Clockaerts
Yvonne M
YM
Bastiaansen-Jenniskens
Carola
C
Feijt
Luc
L
De Clerck
J A N
JA
Verhaar
Anne-Marie
AM
Zuurmond
Vedrana
V
Stojanovic-Susulic
Johan
J
Somville
Margreet
M
Kloppenburg
Gerjo J V M
GJ
van Osch
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D015232:Dinoprostone / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D020738:Leptin / Q000235:genetics; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000276:immunology*; D047493:PPAR alpha / Q000819:agonists*; D010329:Patella; D011743:Pyrimidines / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D000924:Anticholesteremic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; C508609:IL10 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D020738:Leptin; D047493:PPAR alpha; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; C006253:pirinixic acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone