The infrapatellar fat pad is affected by injury induced inflammation in the rabbit knee: use of dexamethasone to mitigate damage

• Published in: Inflammation research Vol. 65; no. 6; pp. 459 - 470
• Main Authors: Heard, Bryan J., Solbak, Nathan M., Chung, May, Achari, Yamini, Shrive, Nigel G., Frank, Cyril B., Hart, David A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2016; Springer Nature B.V
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - pathology; Allergology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cytokines - genetics; Cytokines - metabolism; Dermatology; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Female; Fibrosis; Immunology; Injections, Intra-Articular; Knee Injuries - complications; Knee Injuries - drug therapy; Knee Injuries - pathology; Knee Joint - drug effects; Knee Joint - pathology; Leptin - genetics; Neurology; Original Research Paper; Pharmacology/Toxicology; Rabbits; Rheumatology; RNA, Messenger - metabolism; Vascular Endothelial Growth Factor A - genetics; Rabbit model; Inflammation; Dexamethasone; Glucocorticoid; Knee injury; Infrapatellar fat pad
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-016-0928-z

Objective and design
The health of the infrapatellar fat pad (IFP) has been linked to pain, joint inflammation, and the onset of post-traumatic osteoarthritis. Thus, early inflammation effects on the IFP could have long term sequelae on joint integrity. This study was designed to characterize the natural history of the IFP in a model of surgically induced knee injury and inflammation, and to test the efficacy of one intra-articular (IA) administration of dexamethasone (DEX) immediately following surgery.
Methods
An IA bone drill hole injury to the rabbit knee was conducted and immediately treated with DEX (
n
 = 12). Early and late post-surgical time-points were investigated (48 h and 9 weeks) and the outcome measures were analysis of IFP histology, mRNA levels for relevant molecules, and protein levels for a subset of cytokines. Data were analyzed against a surgical control (injury without treatment;
n
 = 12), a surgical sham (capsular incision only;
n
 = 12), and normal control (
n
 = 6).
Treatment
Single IA injection of DEX (0.5 mg/kg), administered at the completion of surgery.
Results
IFPs from injured joints exhibited significantly increased cellularity and early fibrosis at 48 h post surgery. While the histological inflammation from a capsular incision alone resolved, knee injured animals progressed to a significantly more fibrotic IFP by 9 weeks. DEX significantly lowered histological scores at 48 h, but not at the 9 weeks. DEX did not influence mRNA levels for IL-1β, 6, and 8, however, protein analysis indicated that IL-8 levels were lower in DEX treated joints. DEX resulted in significantly elevated expression of mRNA for MCP-1, leptin, and VEGF.
Conclusion
One IA administration of a glucocorticoid appears to mitigate the initial inflammation within the joint, but is not sufficient to protect the joint to 9 weeks post-surgery.