Mechanism of increased lung injury after acute pancreatitis in IL-10 knockout mice.
BACKGROUND
IL-10 is a potent anti-inflammatory cytokine which inhibits inflammatory cytokine release from all tissue sites. Hepatic cytokine release from Kupffer cells (KC) is one important source of inflammatory cytokines and may be the main one causing lung damage in acute pancreatitis (AP). Here we studied the KC contribution to lung injury in IL-10 knockout (KO) mice, in which tissue inflammatory cytokine release from all sites is unrestrained, and AP is more severe.


METHODS
Three- to 4-week-old C57BL/6J mice and KO mice on a C57BL/6J background were used. Control mice received regular chow and gadolinium chloride (GD; 1 mg/100 g iv), to inhibit KC activity, or saline. Pancreatitis mice received a choline-deficient, ethionine-supplemented diet for 66 h to induce AP and saline or GD injections iv. After 66 h, lung tissue was assessed for edema, myeloperoxidase (MPO), and superoxide dismutase (SOD). Histology was scored in a blinded fashion.


RESULTS
In pancreatitis KO mice, KC blockade had no effect on the degree of lung edema, lung neutrophil infiltration, and lung histology score. As expected, each of these parameters was more severe in the KO mice than in the normal mice: lung wet/dry ratio 5.3 +/- 0.2 versus 4.3 +/- 0.13; lung MPO (U/g) 1.9 +/- 0.2 versus 1.1 +/- 0.08; histology score 7.1 +/- 0.8 versus 5.3 +/- 0.5.


CONCLUSIONS
Endogenous IL-10 is important in reducing the lung injury in this model of AP. KC-derived cytokines were of minor importance, compared to those derived from all other tissue sites.
Gloor
B
B
Department of Surgery, UCLA School of Medicine, Los Angeles, California, 90095, USA.
Todd
K E
KE
Lane
J S
JS
Rigberg
D A
DA
Reber
H A
HA
D000208:Acute Disease; D000818:Animals; D005260:Female; D016753:Interleukin-10 / Q000235:genetics*; D007728:Kupffer Cells / Q000502:physiology; D008168:Lung / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D009504:Neutrophils / Q000473:pathology; D010195:Pancreatitis / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
D016753:Interleukin-10; D009195:Peroxidase; D013482:Superoxide Dismutase