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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2003 Feb;62(2):108–112. doi: 10.1136/ard.62.2.108

Cytokine production in the infrapatellar fat pad: another source of cytokines in knee synovial fluids

T Ushiyama 1, T Chano 1, K Inoue 1, Y Matsusue 1
PMCID: PMC1754438  PMID: 12525378

Abstract

Background: Recent studies have shown that adipose tissue is an endocrine organ that releases various cytokines.

Objective: To investigate the production of growth factors and proinflammatory cytokines in infrapatellar fat pad specimens.

Methods: Infrapatellar fat pad tissues were obtained from patients during knee surgery. Protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)α, and interleukin (IL)6 in homogenised tissues were measured by an enzyme immunoassay. Gene expressions for those cytokines were examined by reverse transcription-polymerase chain reaction (RT-PCR). Localisation of bFGF and VEGF was evaluated by immunohistochemistry and in situ hybridisation.

Results: Infrapatellar fat pads were found to contain various protein levels of bFGF, VEGF, TNFα, and IL6. Further, gene expressions for these cytokines were detected by RT-PCR. Immunohistochemistry and in situ hybridisation showed that the expressions of both bFGF and VEGF were localised in immature adipocytes, interstitial undifferentiated mesenchymal cells, and vascular endothelial cells.

Conclusion: The production of bFGF, VEGF, TNFα, and IL6 in the infrapatellar fat pad was demonstrated. Although synovial cells and articular chondrocytes are thought to be primary sources of cytokines found in knee synovial fluids, the results suggest that they may also originate from this fat pad.

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Figure 1.

Figure 1

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RT-PCR results for bFGF, VEGF, TNFα, IL6, and GAPDH in infrapatellar fat pad tissues. Expected sizes of the amplified DNA fragments are shown in the ethidium bromide 6% polyacrylamide gel electrophoresis images. The number under each panel indicates patient number, whose characteristics are shown in table 1. Amplified fragments of bFGF, the lower three VEGF isoforms (VEGF121: 516 bp, VEGF165: 648 bp, VEGF189: 720 bp), and TNFα were detected in all five specimens, whereas those of IL6 were detected in only one.

Figure 2.

Figure 2

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Immunohistochemical staining of infrapatellar fat pad tissues. (A) bFGF, (B) VEGF, (C) normal rabbit IgG. Positive cytoplasmic staining for bFGF and VEGF was detected in relatively immature adipocytes, interstitial undifferentiated mesenchymal cells, and vascular endothelial cells. Original magnification x100.

Figure 3.

Figure 3

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In situ hybridisation results for bFGF and VEGF in infrapatellar fat pad tissues. (A) Anti-sense probe for bFGF, (B) sense probe for bFGF, (C) anti-sense probe for VEGF, (D) sense probe for VEGF. Positive signals for bFGF and VEGF were detected in the cytoplasm of relatively immature adipocytes, interstitial undifferentiated mesenchymal cells, and vascular endothelial cells. Original magnification x50.

Selected References

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