Persistent Release of IL-1s from Skin Is Associated with Systemic Cardio-Vascular Disease, Emaciation and Systemic Amyloidosis: The Potential of Anti-IL-1 Therapy for Systemic Inflammatory Diseases
Figure 2
IL-1α and IL-1β trigger fat tissue remodeling.
A) KCASP1Tg mice were treated once-a-week with an intra-peritoneal injection of 10 µg anti-IL-1α and/or IL-1β neutralizing antibodies between 4 to 24 weeks of age. PBS-treated KCASP1Tg littermates were used as controls. The body weight loss was ameliorated by either anti-IL-1α, anti-IL-1β or anti-IL-1α/β administration, (n = 7, each group). B) Emaciation was reproduced by administering 1 µg of recombinant IL-1α or IL-1β protein 3 times per week from 6 to 16 weeks of age to wild type mice compared to PBS-injected mouse controls from 6 to 16 weeks (n = 6, each group). C) H&E staining of abdominal adipose tissue revealed that the adipocytes were large and plump in shape in normal control and 6-months old KIL-18Tg(−) mice; they were small and round, however, in 6-month-old KCASP1Tg and 18-months old KIL-18Tg(+) mice. The number of infiltrating mononuclear cells was similar among these groups (n = 7, each group). D) Cytokine levels in the skin culture supernatant were measured by flow cytometry. IL-1α and IL-1β were detected in conditioned medium from the skin culture of normal control mice and KIL-18Tg(−) mice, but was significantly higher in medium from skin culture of KCASP1Tg mice (n = 7, each group). E) Mouse adipose cells cultured in regular medium contained abundant lipid drops on day 14. The addition of supernatant from normal skin culture revealed a decrease in the number of plump adipocytes containing lipids as stained with oil red O, which was reversed by supplementing with supernatant from KCASP1Tg mice skin culture. The pretreatment of KCASP1Tg mice skin culture medium with anti-IL-1α or anti-IL-1β neutralizing antibodies partially ameliorated the inhibitory effects on adipose cells, which were almost abrogated by simultaneous treatment with both antibodies (n = 7, each group).