To provide a comprehensive immunohistochemical (IHC) map of the temporal expression and tissue distribution of interleukin-1β (IL-1β) through progression of osteoarthritis (OA) in two strains of guinea pigs with varying propensity for spontaneous knee joint disease.
OA-prone Hartley and OA-resistant Strain 13 guinea pigs were collected at 60, 120, 180, 240, 360, and 480 days of age (N=4 animals per strain per date). IHC was performed on whole joint preparations; the distribution of IL-1β expression on coronal sections was mapped, semi-quantitatively scored, and correlated to OA grade using Mankin criteria with guinea pig-specific modifications. OA and IHC indices were compared among times and between strains using the Kruskal-Wallis one-way analysis of variance by ranks followed by Dunn's post test.
OA indices for both strains increased from 60 to 480 days of age; a statistically higher score (P ≤ 0.01) was found in Hartley animals at 180, 240, 360, and 480 days. At 60 days of age, IL-1β expression was detected in cartilage, menisci, synovium, and subchondral bone in both strains. Persistent and statistically increased (P<0.05) IL-1β expression was found in these same tissues in Hartley animals at 120 and 180 days, while Strain 13 animals demonstrated a significant reduction in positive immunostaining. Statistical differences in IHC indices between strains beyond 240 days of age were restricted to synovium (days 240 and 480) and subchondral bone (days 360 and 480).
As expected, histologic OA proceeded in an accelerated manner in Hartley animals relative to Strain 13 animals. The OA-prone strain did not demonstrate reduced IL-1β expression during adult maturity as occurred in the OA-resistant strain, and this persistent expression may have corresponded to early incidence of OA. Future interventional studies are warranted to explore whether dysregulation of IL-1β expression may contribute to premature onset of spontaneous disease in the Hartley guinea pig.