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Influence of dietary (n-3)-polyunsaturated fatty acids on leukotriene B4 and prostaglandin E2 synthesis and course of experimental tuberculosis in guinea pigs

Einfluß einer Diät mit (n-3)-mehrfach ungesättigten Fettsäuren auf die Leukotrien B4- und Prostaglandin E2-Synthese und den Verlauf der experimentellen Tuberkulose bei Meerschweinchen

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Summary

In the present study eicosanoid synthesis was studied in macrophages of guinea pigs fed different amounts of (n-6)- and (n-3)-polyunsaturated fatty acids (PUFA). Three groups of weanling guinea pigs were fed by isocaloric diets differing only in their contents of PUFA: controls with 2.8 Cal% of linoleic acid (LA; 18:2(n-6)); (n-6)-rich fed animals with 15.4 Cal% of LA; and (n-3)-rich fed animals with 10.1 Cal% of LA, 1.4 Cal% of eicosapentaenoic acid (20:5(n-3)) and docosahexaenoic acid (22:6(n-3)). After 13 weeks half the number of animals from each group was infected i.m. by 180 colony forming units ofMycobacterium tuberculosis strain H37Rv. Seven weeks after infection the release of leukotriene (LT)B4 and prostaglandin (PG)E2 was quantified in calcium ionophore stimulated whole blood, peritoneal macrophage cultures and alveolar macrophages by immunoassays after high performance liquid chromatography. Synthesis of LTB4 and PGE2 was found to be reduced in (n-3)-rich fed guinea pigs (p<0.05), and equivalent between controls and (n-6)-rich fed animals. Controls and (n-6)-rich fed animals showed the same mycobacterial counts in the spleen whereas (n-3)-rich fed guinea pigs demonstrated an increased number of mycobacteria (p<0.05). Our results demonstrate that an increased dietary intake of (n-3)-PUFA suppress LTB4 and PGE2 synthesis. The increased number ofM. tuberculosis found in the spleens of (n-3)-rich fed animals could represent persistence of the experimental infection. It may be speculated that a functional relationship exists between the two findings.

Zusammenfassung

In der vorliegenden Studie wurde die Eikosanoidsynthese in Makrophagen von Meerschweinchen untersucht, die mit unterschiedlichen Gehalten (n-6)- und (n-3)-mehrfach ungesättigten Fettsäuren (PUFA) gefüttert wurden. Drei Gruppen entwöhnter Meerschweinchen wurden mit isokalorischen Diäten gefüttert, die sich nur in ihrem Gehalt an PUFA unterschieden: Kontrollen mit 2,8 Cal% Linolsäure (LA. (18:2(n-6)); Tiere mit (n-6)-angereichertem Futter mit 15,4 Cal% LA und Tiere mit (n-3)-angereichertem Futter mit 10,1 Cal% LA, 1,4 Cal% Eikosapentaensäure (20:5(n-3)) und 0,9 Cal% Dokosahexaensäure (22:6(n-3)). Nach 13 Wochen wurde die Hälfte der Tiere aus jeder Gruppe mit 180 Kolonie-bildenden Einheiten des StammesMycobacterium tuberculosis H37Rv i.m. infiziert. Sieben Wochen nach Infektion wurde die Freisetzung von LTB4 und PGE2 in Kalzium-Ionophor stimuliertem Vollblut, Peritonealmakrophagen und Alveolarmakrophagen mittels Immunoassays nach Hochdruckflüssigkeitschromatographie quantifiziert. Die Synthese von LTB4 und PGE2 war reduziert bei den (n-3)-reich gefütterten Meerschweinchen (p<0,05) und äquivalent bei den Kontrollen und (n-6)-reich gefütterten Tieren. Kontrolltiere und (n-6)-reich gefütterte Meerschweinchen wiesen die gleiche Zahl von Mykobakterien in der Milz auf, während sich bei den (n-3)-gefütterten Tieren eine erhöhte Zahl von Mykobakterien zeigte (p<0,05). Unsere Ergebnisse zeigen, daß eine höhere diätetische Zufuhr von (n-3)-PUFA die Synthese von LTB4 und PGE2 unterdrückt. Die erhöhte Zahl vonM. tuberculosis in den Milzen von (n-3)-gefütterten Tieren spricht für eine Persistenz der experimentellen Tuberkulose unter diesen Bedingungen. Möglicherweise existiert zwischen beiden Befunden ein funktioneller Zusammenhang.

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References

  1. Knapp, H. R., Reilly, I. A. G., Alessandrini, P., Fitzgerald G. A. In vitro indexes of platelet and vascular function during fish oil administration in patients with atherosclerosis. N. Engl. J. Med. 314 (1986) 937–942.

    Google Scholar 

  2. Leslie, C. A., Gonnermann, W. A., Ullman, M. D., Hayes, K. C., Franzblau, C., Cathcart, E. S. Dietary fish oil modulates macrophage fatty acids and decreases arthritis susceptibility in mice. J. Exp. Med. 182 (1985) 1336–1349.

    Google Scholar 

  3. Kelley, D. S., Dougherty, R. M., Branch, L. B., Taylor, P. C., Jacono, J. M. Concentration of dietary n-6 polyunsaturated fatty acids and the human immune status. Clin. Immunol. Immunopathol. 2 (1992) 240–244.

    Google Scholar 

  4. Kremer, J. M., Lawrence, D. A., Jubiz, W., DiGiacomo, R., Rynes, R., Bartholomew, L. E., Sherman, M. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis: clinical and immunological effects. Arthritis Rheum. 33 (1990) 810–820.

    Google Scholar 

  5. Kromhout, D., Boschieter, E. B., De Lezemme Coulander, C. The inverse relationship between fish consumption and 20 year mortality from coronary heart disease. N. Engl. J. Med. 116 (1985) 433–435.

    Google Scholar 

  6. Chang, H. R., Bullo, A. G., Gladoianu, P. F., Arsenijevic, D., Girardier, L., Pechere, J. C. Fish oil decreases natural resistance of mice to infection withSalmonella typhimurium. Metabolism 41 (1991) 1–2.

    Google Scholar 

  7. Bhaskaram, P., Sundaramma, M. N. Peripheral blood monocyte function in malnourished subjects with pulmonary tuberculosis. Eur. J. Clin. Nutr. 44 (1990) 248–254.

    Google Scholar 

  8. Chanarin, I., Stephenson, E. Vegetarian diet and cobalamin deficiency: their association with tuberculosis. J. Clin. Pathol. 41 (1988) 759–762.

    Google Scholar 

  9. Rook, G. A. W., Taverne, J., Leveton, C., Steele, J. The role of gamma-interferon, vitamin D3 metabolites, and TNF in the pathogenesis of tuberculosis. Immunol. 62 (1987) 229–234.

    Google Scholar 

  10. McMurray, D. N., Bartow, R. A., Mintzer, C. L. Protein malnutrition alters the distribution of FcγR+(Tγ) and FcμR+(Tμ)T lymphocytes in experimental pulmonary tuberculosis. Infect. Immun. 58 (1990) 563–565.

    Google Scholar 

  11. Drevon, C. A. Marine oils and their effects. Nutr. Rev. 50 (1992) 38–45.

    Google Scholar 

  12. Gibson, R. A., Neumann, M. A., James, M. J., Hawkes, J. S., Hall, C., Cleland, L. G. Effect of n-3 and n-6 dietary fats on the lipoxygenase products from stimulated rat neutrophils. Prostaglandins Leukot. Essent. Fatty Acids 46 (1992) 87–91.

    Google Scholar 

  13. Lee, T. H., Hoover, R. L., Williams, J. D., Sperling, R. I., Ravalese, J. III., Spur, B. W., Robinson, D. R., Corey, E. J., Lewis, R. A., Austen, K. F. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids onin vitro neutrophil and monocyte leukotriene generation and neutrophil function. N. Engl. J. Med. 312 (1985) 1217–1224.

    Google Scholar 

  14. Garg, M. I., Thomson, A. B. R., Clandinin, M. T. Interactions of saturated, n-6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism. J. Lipid Res. 31 (1990) 271–277.

    Google Scholar 

  15. German, J. N., Bruckner, G. G., Lokesh, B., Kinsella, J. E. Effects of increasing levels of dietary fish oil on tissue lipid composition and prostaglandin synthesis in the rat. Nutr. Res. 35 (1985) 512–517.

    Google Scholar 

  16. Leitch, A. G., Lee, T. H., Ringel, E. W., Prickett, J. E., Robinson D. R., Pyne, S. G., Corey, E. J., Dazen, J. M., Austen, K. F., Lewis, R. A. Immunologically induced generation of tetraene and pentaene leukotrienes in the peritoneal cavities of menhaden oil fed rats. J. Immunol. 132 (1984) 2559–2565.

    Google Scholar 

  17. Kaplan, G. J., Fraser, R. I., Comstock, G. W. Tuberculosis in Alaska 1970. Am. Rev. Respir. Dis. 105 (1971) 920–926.

    Google Scholar 

  18. Bang, H. O., Dyerberg, J. Lipid metabolism and ischemic heart disease in Greenland Eskimos. Adv. Nutr. Res. 3 (1980) 1–22.

    Google Scholar 

  19. Lokesh, B. R., Black, J. M., German, J. B., Kinsella, J. E. Docosahexaenoic acid and other dietary polyunsaturated fatty acids suppress leukotriene synthesis by mouse peritoneal macrophages. Lipids 23 (1988) 968–972.

    Google Scholar 

  20. Samuelsson, B., Dahlen, S.-E., Lindgren, J. A., Rouzer, C. A., Serhan, C. N. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237 (1987) 1171–1176.

    Google Scholar 

  21. Phipps, R. P., Stein, S. H., Roper, R. L. A new view of prostaglandin E regulation of the immune response. Immunol. Today 12 (1991) 349–352.

    Google Scholar 

  22. Grover, A. A., Kim, H. K., Wiegeshaus, E. H., Smith, D. W. Hostparasite relationship in experimental airborne tuberculosis. II. Reproducible infection by means of an inoculum preserved at −70°C. J. Bacteriol. 94 (1967) 832–835.

    Google Scholar 

  23. Balasubramanian, V., Guo-Zhi, W., Wiegeshaus, E., Smith, D. Virulence ofMycobacterium tuberculosis for guinea pigs: a quantitative modification of the assay developed byMitchinson. Tubercle Lung Dis. 73 (1992) 268–272.

    Google Scholar 

  24. Tateson, J. E., Randall, R. W., Reynolds, C. H., Jackson, W. P., Bhattacherjee, P., Salmon, J. A., Garland, L. G. Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: biochemical assessmentin vitro andex vivo. Br. J. Pharmacol. 94 (1988) 528–539.

    Google Scholar 

  25. Saltini, C., Hance, A. J., Ferrans, V. J., Basset, F., Bitterman P. B., Crystal, R. G. Accurate quantification of cells recovered by bronchoalveolar lavage. Am. Rev. Respir. Dis. 130 (1984) 650–658.

    Google Scholar 

  26. Guhlmann, A., Keppler, A., Kästner, S., Krieter, H., Brückner, U. B., Messmer, K., Keppler, D. Prevention of endogenous leukotriene production during anaphylaxis in the guinea pig by an inhibitor of leukotriene biosynthesis (MK-886) but not by dexamethasone. J. Exp. Med. 170 (1989) 1905–1918.

    Google Scholar 

  27. Mayatepek, E., Lehmann, W.-D., Fauler, J., Tsikas, D., Frölich, J. C., Schutgens, R. B. H., Wanders, R. J. A., Keppler, D. Impaired degradation of leukotrienes in patients with peroxisome deficiency disorders. J. Clin. Invest. 91 (1993) 881–888.

    Google Scholar 

  28. Gurr, M. I. The role of lipids in the regulation of the immune system. Prog. Lipid Res. 22 (1983) 257–287.

    Google Scholar 

  29. Locksley, R. M., Fankhauser, J., Henderson, W. R. Alteration of leukotriene release by macrophages ingestingToxoplasma gondii. Proc. Natl. Acad. Sci. USA 82 (1985) 6922–6926.

    Google Scholar 

  30. Huang, S. C., Misfeldt, M. L., Fritsche, K. L. Dietary fat influences Ia antigen expression and immune cell populations in the murine peritoneum and spleen. J. Nutr. 122 (1992) 1219–1231.

    Google Scholar 

  31. Engels, W., Lemmens, P. J. M. R., Muller, A. D., Van Dam-Mieras, M. C. E., Hornstra, G. The effect of viral infection on eicosanoid formation and procagulant activity of rat peritoneal macrophages. Eicosanoids 5 (1992) 73–80.

    Google Scholar 

  32. Klickstein, L., Shapleigh, C., Goetzl, E. Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondylarthritis. J. Clin. Invest. 66 (1980) 1166–1170.

    Google Scholar 

  33. Stenson, W. F., Cort, D., Rodgers, J. Dietary supplementation with fish oil in ulcerative colitis. Ann. Intern. Med. 116 (1992) 609–614.

    Google Scholar 

  34. Lawrence, R., Sorrell, T. Eicosapentaenoic acid in cystic fibrosis: evidence of a pathogenetic role for leukotriene B4. Lancet 342 (1993) 465–469.

    Google Scholar 

  35. Rola-Pleszczynski, M., Chavaillaz, P. A., Lemaire, I. Stimulation of interleukin 2 and interferon-γ production by leukotriene B4 in human lymphocyte cultures. Prostaglandins Leukot. Med. 23 (1986) 207–210.

    Google Scholar 

  36. Yamashita, N., Sugiyama, E., Hamazaki, T., Yano, S. Inhibition of natural killer cell activity by eicosapentaenoic acidin vivo andin vitro. Biochem. Biophys. Res. Comm. 150 (1988) 497–505.

    Google Scholar 

  37. Kunkel, S. L., Chensue, S. W., Mouton, C. Role of lipoxygenase products in murine pulmonary granuloma formation. J. Clin. Invest. 74 (1984) 514–524.

    Google Scholar 

  38. Kaufmann, S. H. E., Flesch, I. E. A. The role of T cell-macrophage interactions in tuberculosis. Springer Semin. Immunopathol. 10 (1988) 337–358.

    Google Scholar 

  39. Montreewasuwat, N., Curtis, J., Turk, J. L. Interleukin 1 and prostaglandin production by cells of the mononuclear phagocyte system isolated from mycobacterial granulomas. Cell. Immunol. 104 (1987) 12–23.

    Google Scholar 

  40. Kindler, V., Sappino, A.-P., Grau, G. E., Piguet, P.-F., Vassalli, P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 56 (1989) 731–740.

    Google Scholar 

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Mayatepek, E., Paul, K., Leichsenring, M. et al. Influence of dietary (n-3)-polyunsaturated fatty acids on leukotriene B4 and prostaglandin E2 synthesis and course of experimental tuberculosis in guinea pigs. Infection 22, 106–112 (1994). https://doi.org/10.1007/BF01739016

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