Modulation of Human Hepatocyte Acute Phase Protein Production In Vitro by n-3 and n-6 Polyunsaturated Fatty Acids

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Abstract
Objective The authors investigate the role of a variety of essential polyunsaturated fatty acids on the spontaneous and interleukin-6 stimulated production of acute phase proteins by isolated human hepatocytes. Summary Background Data The altered production of acute phase proteins by the liver is one of the principal effects of the systemic inflammatory response in human disease. It has been shown that polyunsaturated fatty acids have certain anti-inflammatory properties that potentially are mediated through altered prostaglandin or proinflammatory cytokine production. However, the effect of polyunsaturated fatty acids on the responsiveness of the human hepatocyte to proinflammatory cytokines has not been studied in detail. Methods Hepatocytes isolated from human livers were maintained in primary culture in the presence of a variety of bovine serum albumin-complexed fatty acids. The influence of these fatty acids on hepatocyte acute phase protein production was assessed, in the presence and absence of recombinant interleukin-6, by measurement of acute phase proteins by enzyme-linked immunosorbent assay. Results Eicosapentaenoic and gammalinolenic acid increased spontaneous production of α1-antichymotrypsin and prealbumin but decreased spontaneous production of transferrin and haptoglobin from isolated human hepatocytes. Eicosapentaenoic and gammalinolenic significantly increased interleukin-6-stimulated production of C-reactive protein and α1-antichymotrypsin but reversed the stimulatory effect of interleukin-6 on haptoglobin production. These fatty acids also reversed the inhibitory effect of interleukin-6 on prealbumin production. Conclusions These results show that certain fatty acids have the potential to modulate spontaneous and cytokine-induced alterations in human hepatic acute phase protein metabolism. These data indicate the presence of complex mechanisms of regulation of human hepatic protein metabolism by fatty acids, and further study will be required to establish the nature of their influence in vivo.

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