Development of intestinal inflammation in double IL-10- and leptin-deficient mice.
Leptin-deficient (ob/ob) mice are resistant in different models of autoimmunity and inflammation, suggesting that leptin regulates immunity and inflammation. To investigate whether leptin deficiency modulates the spontaneous intestinal inflammation observed in interleukin (IL)-10-deficient mice, double IL-10- and leptin-deficient [IL-10 knockout (KO) ob/ob] mice were generated and compared with single IL-10 KO mice for colitis severity. Body weight in IL-10 KO ob/ob mice was significantly reduced compared with that of ob/ob mice. However, when compared with wild-type or IL-10 KO mice, IL-10 KO ob/ob mice were still markedly obese. IL-10 KO and IL-10 KO ob/ob mice developed colitis with a comparable time-course and severity in terms of macroscopic and histologic scores. Likewise, production of interferon-gamma, IL-6, and IL-13 from colon cultures and splenocytes did not differ among these two groups. Conversely, rates of apoptosis were higher in lamina propria lymphocytes obtained from the colon of IL-10 KO ob/ob compared with IL-10 KO mice. In conclusion, although leptin deficiency has been associated with resistance in models of autoimmunity and inflammation induced by exogenous stimuli, leptin appears not to play a significant role in the spontaneous colitis of IL-10 KO mice, although it modulates survival of intestinal lymphocytes.
Siegmund
Britta
B
Charité Universitaetsmedizin Berlin, Campus Benjamin Franklin, Germany.
Sennello
Joseph A
JA
Lehr
Hans A
HA
Batra
Arvind
A
Fedke
Inka
I
Zeitz
Martin
M
Fantuzzi
Giamila
G
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D002455:Cell Division; D002478:Cells, Cultured; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D018793:Interleukin-13 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D020738:Leptin / Q000235:genetics / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism
D018793:Interleukin-13; D015850:Interleukin-6; D020738:Leptin; D016753:Interleukin-10; D007371:Interferon-gamma