Objective
Rheumatoid arthritis is a chronic inflammatory condition resulting in joint destruction and extra-articular morbidities. Caffeic acid phenethyl ester (CAPE) is an NF-kappa B inhibitor with anti-inflammatory and immunomodulatory properties.
Aim: To determine the effect of CAPE treatment on histological indicators of joint inflammation, bone loss and gastrointestinal inflammation associated with CAIA.
Methods
Balb/c mice were allocated to four groups of n=8; control, CAPE (1mg/kg), CAIA and CAIA+CAPE (1mg/kg). Tissues were harvested after 14 days. Paw sections were stained with haematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) and assessed for joint inflammation, cartilage and bone damage. Jejunum and colon tissue was stained with H&E and alcian blue periodic acid-Schiff to assess histopathological damage and goblet cell number, respectively. All analysis was conducted in a blinded fashion.
Results
CAIA and CAIA+CAPE joint tissues exhibited greater cellular infiltration, cartilage and bone degradation and pannus formation scores, however compared to controls these were not statistically significant. A significantly greater number of multinucleated TRAP-positive cells was observed in bone and surrounding soft tissue in the paws of CAIA (p=0.029 and p=0.005) and CAIA+CAPE mice (p=0.003 and p=0.024), compared to control and CAPE only mice. The number of multinucleated TRAP-positive cells did not significantly differ between CAIA and CAIA+CAPE mice. Neither CAPE nor CAIA affected the jejunum toxicity score compared to controls. CAIA mice significantly increased colon toxicity scores compared to control mice (p=0.023). CAIA+CAPE mice exhibited a reduced toxicity score and reduced percentage of cavitated goblet cells in the colon crypts compared with CAIA mice (p=0.026 and p=0.003, respectively).
Conclusions
CAPE treatment did not reduce joint inflammation or bone loss in CAIA mice. Specific gastrointestinal changes were observed in the colon of CAIA+CAPE mice, however low dose CAPE treatment did not significantly alter the histopathology in the jejunum of CAIA mice.