The lack of sensitive and relatively non-invasive measures has hampered monitoring the
clinical course of spontaneously developing
colitis in IL-2-deficient (-/-) mice. We selected (i) to study the correlation of the acute phase
plasma proteins serum amyloid A (SAA) and
serum amyloid P component (SAP) levels with
colonic disease and (ii) to characterize the
amyloidosis in the IL-2(-/-)animals. IL-2(-/-)mice exhibited increasing severity of gross intestinal
inflammation with age, confined to the distal colon. Histologically, the
colonic disease score increased serially in IL-2(-/-)animals. Wild-type mice showed no activity, while 16-week-old IL-2(+/-)animals had minimal
colitis with small
ulcers and lamina propria inflammatory infiltrate. Periportal
hepatitis was present and positive
Congo red staining indicated
amyloidosis of the liver and spleen in 16 week IL-2(-/-)mice. SAA immunostaining in the liver and spleen was increased in the 8 week and 16 week IL-2(-/-)and 16 week IL-2(+/-)animals indicating AA
amyloid deposits. Plasma SAA and SAP levels were markedly elevated, and generally preceded the onset of
colitis and reflected its severity. Northern analysis showed markedly increased SAA expression in the liver and intestine of IL-2(-/-)and intestine of IL-2(+/-)16-week-old animals. Increased intestinal expression of SAA3 (lamina propria macrophages) indicates local
inflammation in IL-2(+/-)animals at 16 weeks. Treatment of 3-week-old animals with systemic
IL-2 or
IL-1 receptor antagonist (IL-1ra) delayed
inflammation, postponed the increase in SAA levels and minimized disease onset. These results further demonstrate that
IL-2 plays a significant role in normal immune responses in the body and that plasma SAA levels both reflect
colonic disease severity and may indicate subclinical disease in both IL-2(-/-)and IL-2(+/-)mice. Furthermore. The mechanism of IL-2-deficient induced
colitis appears to be mediated in part through the increase in
IL-1. In addition, the IL-2(-/-)mouse of spontaneous
enterocolitis may provide a unique system for studying spontaneously developing
AA amyloidosis.