Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1985 Oct 1;162(4):1336–1349. doi: 10.1084/jem.162.4.1336

Dietary fish oil modulates macrophage fatty acids and decreases arthritis susceptibility in mice

PMCID: PMC2187871  PMID: 3930652

Abstract

B10.RIII and B10.G mice were transferred from a diet of laboratory rodent chow to a standard diet in which all the fat (5% by weight) was supplied as either fish oil (17% eicosapentaenoic acid [EPA], 12% docosahexaenoic acid [DHA], 0% arachidonic acid [AA], and 2% linoleic acid) or corn oil (0% EPA, 0% DHA, 0% AA, and 65% linoleic acid). The fatty acid composition of the macrophage phospholipids from mice on the chow diet was similar to that of mice on a corn oil diet. Mice fed the fish oil diet for only 1 wk showed substantial increases in macrophage phospholipid levels of the omega-3 fatty acids (of total fatty acid 4% was EPA, 10% docosapentaenoic acid [DPA], and 10% DHA), and decreases in omega-6 fatty acids (12% was AA, 2% docosatetraenoic acid [DTA], and 4% linoleic acid) compared to corn oil-fed mice (0% EPA, 0% DPA, 6% DHA, 20% AA, 9% DTA, and 8% linoleic acid). After 5 wk this difference between the fish oil-fed and corn oil-fed mice was even more pronounced. Further small changes occurred at 5-9 wk. We studied the prostaglandin (PG) and thromboxane (TX) profile of macrophages prepared from mice fed the two diets just before being immunized with collagen. Irrespective of diet, macrophages prepared from female mice and incubated for 24 h had significantly more PG and TX in the medium than similarly prepared macrophages from male mice. The increased percentage of EPA and decreased percentage of AA in the phospholipids of the macrophages prepared from the fish oil-fed mice was reflected in a reduction in the amount of PGE2 and PGI2 in the medium relative to identically incubated macrophages prepared from corn oil-fed mice. When this same fish oil diet was fed to B10.RIII mice for 26 d before immunization with type II collagen, the time of onset of arthritis was increased, and the incidence and severity of arthritis was reduced compared to arthritis induced in corn oil-fed mice. The females, especially those on the fish oil diet, tended to have less arthritis than the males. These alterations in the fatty acid pool available for PG and leukotriene synthesis suggest a pivotal role for the macrophage and PG in the immune and/or inflammatory response to type II collagen.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bang H. O., Dyerberg J., Hjøorne N. The composition of food consumed by Greenland Eskimos. Acta Med Scand. 1976;200(1-2):69–73. doi: 10.1111/j.0954-6820.1976.tb08198.x. [DOI] [PubMed] [Google Scholar]
  2. Bockman R. S. Prostaglandin production by human blood monocytes and mouse peritoneal macrophages: synthesis dependent on in vitro culture conditions. Prostaglandins. 1981 Jan;21(1):9–31. doi: 10.1016/0090-6980(81)90192-1. [DOI] [PubMed] [Google Scholar]
  3. Bonney R. J., Wightman P. D., Davies P., Sadowski S. J., Kuehl F. A., Jr, Humes J. L. Regulation of prostaglandin synthesis and of the selective release of lysosomal hydrolases by mouse peritoneal macrophages. Biochem J. 1978 Nov 15;176(2):433–442. doi: 10.1042/bj1760433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boraschi D., Censini S., Bartalini M., Scapigliati G., Barbarulli G., Vicenzi E., Donati M. B., Tagliabue A. Interferon inhibits prostaglandin biosynthesis in macrophages: effects on arachidonic acid metabolism. J Immunol. 1984 Apr;132(4):1987–1992. [PubMed] [Google Scholar]
  5. Culp B. R., Titus B. G., Lands W. E. Inhibition of prostaglandin biosynthesis by eicosapentaenoic acid. Prostaglandins Med. 1979 Nov;3(5):269–278. doi: 10.1016/0161-4630(79)90068-5. [DOI] [PubMed] [Google Scholar]
  6. Dyerberg J., Bang H. O., Stoffersen E., Moncada S., Vane J. R. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet. 1978 Jul 15;2(8081):117–119. doi: 10.1016/s0140-6736(78)91505-2. [DOI] [PubMed] [Google Scholar]
  7. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  8. Goodwin J. S., Webb D. R. Regulation of the immune response by prostaglandins. Clin Immunol Immunopathol. 1980 Jan;15(1):106–122. doi: 10.1016/0090-1229(80)90024-0. [DOI] [PubMed] [Google Scholar]
  9. Hagve T. A., Christophersen B. O. Effect of dietary fats on arachidonic acid and eicosapentaenoic acid biosynthesis and conversion to C22 fatty acids in isolated rat liver cells. Biochim Biophys Acta. 1984 Nov 14;796(2):205–217. doi: 10.1016/0005-2760(84)90349-7. [DOI] [PubMed] [Google Scholar]
  10. Kremer J. M., Bigauoette J., Michalek A. V., Timchalk M. A., Lininger L., Rynes R. I., Huyck C., Zieminski J., Bartholomew L. E. Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet. 1985 Jan 26;1(8422):184–187. doi: 10.1016/s0140-6736(85)92024-0. [DOI] [PubMed] [Google Scholar]
  11. Kurland J. I., Bockman R. Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages. J Exp Med. 1978 Mar 1;147(3):952–957. doi: 10.1084/jem.147.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lands W. E., Byrnes M. J. The influence of ambient peroxides on the conversion of 5,8,11,14,17-eicosapentaenoic acid to prostaglandins. Prog Lipid Res. 1981;20:287–290. doi: 10.1016/0163-7827(81)90057-6. [DOI] [PubMed] [Google Scholar]
  13. Lee T. H., Hoover R. L., Williams J. D., Sperling R. I., Ravalese J., 3rd, Spur B. W., Robinson D. R., Corey E. J., Lewis R. A., Austen K. F. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med. 1985 May 9;312(19):1217–1224. doi: 10.1056/NEJM198505093121903. [DOI] [PubMed] [Google Scholar]
  14. Lee T. H., Mencia-Huerta J. M., Shih C., Corey E. J., Lewis R. A., Austen K. F. Effects of exogenous arachidonic, eicosapentaenoic, and docosahexaenoic acids on the generation of 5-lipoxygenase pathway products by ionophore-activated human neutrophils. J Clin Invest. 1984 Dec;74(6):1922–1933. doi: 10.1172/JCI111612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leslie C. A., Levine L. Evidence for the presence of a prostaglandin E 2 -9-keto reductase in rat organs. Biochem Biophys Res Commun. 1973 Jun 8;52(3):717–724. doi: 10.1016/0006-291x(73)90996-0. [DOI] [PubMed] [Google Scholar]
  16. Leslie C. A., Pavlakis A. J., Wheeler J. S., Jr, Siroky M. B., Krane R. J. Release of arachidonate cascade products by the rabbit bladder; neurophysiological significance? J Urol. 1984 Aug;132(2):376–379. doi: 10.1016/s0022-5347(17)49631-5. [DOI] [PubMed] [Google Scholar]
  17. Levine L., Gjtierrez Cernosek R. M., Van Vunakis H. Specificities of prostaglandins B 1 , F 1 , and F 2 antigen-antibody reactions. J Biol Chem. 1971 Nov 25;246(22):6782–6785. [PubMed] [Google Scholar]
  18. Marx J. L. Chemical signals in the immune system. Science. 1983 Sep 30;221(4618):1362–1364. doi: 10.1126/science.6604316. [DOI] [PubMed] [Google Scholar]
  19. Opmeer F. A., Adolfs M. J., Bonta I. L. Regulation of prostaglandin E2 receptors in vivo by dietary fatty acids in peritoneal macrophages from rats. J Lipid Res. 1984 Mar;25(3):262–268. [PubMed] [Google Scholar]
  20. Pawlowski N. A., Kaplan G., Hamill A. L., Cohn Z. A., Scott W. A. Arachidonic acid metabolism by human monocytes. Studies with platelet-depleted cultures. J Exp Med. 1983 Aug 1;158(2):393–412. doi: 10.1084/jem.158.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Popp-Snijders C., Schouten J. A., de Jong A. P., van der Veen E. A. Effect of dietary cod-liver oil on the lipid composition of human erythrocyte membranes. Scand J Clin Lab Invest. 1984 Feb;44(1):39–46. doi: 10.3109/00365518409083785. [DOI] [PubMed] [Google Scholar]
  22. Prickett J. D., Robinson D. R., Steinberg A. D. Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZB x NZW F1 mice. J Clin Invest. 1981 Aug;68(2):556–559. doi: 10.1172/JCI110288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Prickett J. D., Trentham D. E., Robinson D. R. Dietary fish oil augments the induction of arthritis in rats immunized with type II collagen. J Immunol. 1984 Feb;132(2):725–729. [PubMed] [Google Scholar]
  24. Scott W. A., Pawlowski N. A., Andreach M., Cohn Z. A. Resting macrophages produce distinct metabolites from exogenous arachidonic acid. J Exp Med. 1982 Feb 1;155(2):535–547. doi: 10.1084/jem.155.2.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scott W. A., Pawlowski N. A., Murray H. W., Andreach M., Zrike J., Cohn Z. A. Regulation of arachidonic acid metabolism by macrophage activation. J Exp Med. 1982 Apr 1;155(4):1148–1160. doi: 10.1084/jem.155.4.1148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Scott W. A., Zrike J. M., Hamill A. L., Kempe J., Cohn Z. A. Regulation of arachidonic acid metabolites in macrophages. J Exp Med. 1980 Aug 1;152(2):324–335. doi: 10.1084/jem.152.2.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Socini A., Galli C., Colombo C., Tremoli E. Fish oil administration as a supplement to a corn oil containing diet affects arterial prostacyclin production more than platelet thromboxane formation in the rat. Prostaglandins. 1983 May;25(5):693–710. doi: 10.1016/0090-6980(83)90123-5. [DOI] [PubMed] [Google Scholar]
  28. Stenson W. F., Parker C. W. Prostaglandins, macrophages, and immunity. J Immunol. 1980 Jul;125(1):1–5. [PubMed] [Google Scholar]
  29. Stuart J. M., Cremer M. A., Townes A. S., Kang A. H. Type II collagen-induced arthritis in rats. Passive transfer with serum and evidence that IgG anticollagen antibodies can cause arthritis. J Exp Med. 1982 Jan 1;155(1):1–16. doi: 10.1084/jem.155.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tashjian A. H., Jr, Voelkel E. F., Robinson D. R., Levine L. Dietary menhaden oil lowers plasma prostaglandins and calcium in mice bearing the prostaglandin-producing HSDM1 fibrosarcoma. J Clin Invest. 1984 Dec;74(6):2042–2048. doi: 10.1172/JCI111627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Trentham D. E., Townes A. S., Kang A. H. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977 Sep 1;146(3):857–868. doi: 10.1084/jem.146.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vance D. E., Sweeley C. C. Quantitative determination of the neutral glycosyl ceramides in human blood. J Lipid Res. 1967 Nov;8(6):621–630. [PubMed] [Google Scholar]
  33. Whitaker M. O., Wyche A., Fitzpatrick F., Sprecher H., Needleman P. Triene prostaglandins: prostaglandin D3 and icosapentaenoic acid as potential antithrombotic substances. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5919–5923. doi: 10.1073/pnas.76.11.5919. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES