Modulation of pro-inflammatory cytokine biology by unsaturated fatty acids.
Grimble RF. Tappia PS.
Department of Human Nutrition, University of Southhampton, United Kingdom.
The production of pro-inflammatory cytokines, such as interleukins 1 and 6 and tumour necrosis factors, occurs rapidly following trauma or invasion of the body by pathogenic organisms. The cytokines mediate the wide range of symptoms associated with trauma and infection, such as fever, anorexia, tissue wasting, acute phase protein production and immunomodulation. In part, the symptoms result from a co-ordinated response, in which the immune system is activated and nutrients released, from endogenous sources, to provide substrate for the immune system. Although the cytokine mediated response is an essential part of the response to trauma and infection, excessive production of pro-inflammatory cytokines, or production of cytokines in the wrong biological context, are associated with mortality and pathology in a wide range of diseases, such as malaria, sepsis, rheumatoid arthritis, inflammatory bowel disease, cancer and AIDS. Cytokine biology can be modulated by antiinflammatory drugs, recombinant cytokine receptor antagonists and nutrients. Among the nutrients, fats have a large potential for modulating cytokine biology. A number of trials have demonstrated the anti-inflammatory effects of fish oils, which are rich in n-3 polyunsaturated fatty acids, in rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma. Animal studies, conducted by ourselves and others, indicate that a range of fats can modulate pro-inflammatory cytokine production and actions. In summary fats rich in n-6 polyunsaturated fatty acids enhance IL1 production and tissue responsiveness to cytokines, fats rich in n-3 polyunsaturated fatty acids have the opposite effect, monounsaturated fatty acids decrease tissue responsiveness to cytokines and IL6 production is enhanced by total unsaturated fatty acid intake. There are a large number of potential cellular mechanisms which may mediate the effects observed. The majority relate to the ability of fats to alter the composition of membrane phospholipids. As a consequence of alterations in phospholipid composition, membrane fluidity may change, altering binding of cytokines to receptors and G protein activity. The nature of substrate for various signalling pathways associated with cytokine production and actions may also be changed. Consequently, alterations in eicosanoid production and activation of protein kinase C may occur. We have examined a number of these potential mechanisms in peritoneal macrophages of rats fed fats with a wide range of fatty acid composition. We have found that the total C18:2 and 20:4 diacyl species of phosphatidylethanolamine in peritoneal macrophages relates in a positive curvilinear fashion with dietary linoleic acid intake; that TNF induced IL1 and IL6 production relate in a positive curvilinear fashion to linoleic acid intake; that leukotriene B4 production relates positively with dietary linoleic acid intake over a range of moderate intakes and is suppressed at high intakes, while PGE2 production is enhanced. There was no clear relationship between linoleic acid intake and membrane fluidity, however fluidity was influenced in a complex manner by the type of fat in the diet, the period over which the fat was fed and the presence of absence of TNF stimulation. None of the proposed mechanisms, acting alone, can explain the positive effect of dietary linoleic acid intake on pro-inflammatory cytokine production. However each may be involved, in part, in the modulatory effects observed.
Regulation of the LDL receptor gene expression by hormones.
Streicher R. Kotzka J. Muller-Wieland D. Krone W.
Deutsches Institut fur Ernahrungsforschung, Bergholz-Rehbrucke.
Promoter activity of the LDL receptor gene is stimulated by insulin and estradiol and mediated by SRE-1, which acts as a hormone sensitive cis-elemente. Using the antisense technique we reveal that SREBP-1 is selectively involved in the signal transduction pathway of insulin and IGF-I.
Anti-gliadin and anti-endomysium antibodies in children with celiac disease consuming a gluten free diet.
Barna M. Pinter E.
Central Institute for Infectious Diseases, Budapest, Hungary.
A group of 26 children (13 boys and 13 girls; average age 12.2 years) with CD who had been on a gluten free diet for 5-15 years was examined in order to find out how effectively they could manage their diet. The diagnosis of CD was established on the basis of ESPGAN criteria (1969). 5-15 years ago. Antigliadin antibodies, IgG-, and IgA-AGA (by fluorescence enzyme immunoassay), Gliastick by ELISA technique, and Anti-endomysium antibodies (by indirect immunofluorescence on sections of monkey esophagus) were examined in the serum. Only 5 patients had no antigliadin or anti-endomysium antibodies. In 21 cases the IgG-AGA showed positive results; the IgA-AGA was positive in 6, the Gliastick in 19, and the anti-endomysium antibodies in 8 cases. The main cause of the mismanagement of the diet was inadequate food labeling; so it seems to be important to also establish a Food Intolerance Data Bank in Hungary. The 5 sero-negative children volunteered for a gluten challenge; 3 of them became positive in a few weeks or months. Two patients remained negative even after 1 year. Their gluten sensitivity may not prove to be permanent.