Enhanced inflammatory responses in α-tocopherol transfer protein null mice

The liver preferentially secretes α-tocopherol into plasma under the control of the hepatic α-tocopherol transfer protein (α-TTP). α-TTP-null mice (Ttpa−/− mice) are vitamin E deficient, therefore were used for investigations of in vivo responses to sub-normal tissue α-tocopherol concentrations during inflammation. Increased basal oxidative stress in Ttpa−/− mice was documented by increased plasma lipid peroxidation, and superoxide production by bone marrow-derived neutrophils stimulated in vitro with phorbol 12-myristate 13-acetate. Lipopolysaccharide (LPS) injected intraperitoneally induced increases in lung and liver HO-1 and iNOS, as well as plasma NOx in Ttpa+/+ mice. LPS induced more modest increases in these markers in Ttpa−/− mice, while more marked increases in plasma IL-10 and lung lavage TNFα were observed. Taken together, these results demonstrate that α-tocopherol is important for proper modulation of inflammatory responses and that sub-optimal α-tocopherol concentrations may derange inflammatory–immune responses.