Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Post-Transplant Conditions

Oral eicosapentaenoic acid for complications of bone marrow transplantation

Bone Marrow Transplantation volume 28, pages 769–774 (2001)Cite this article

Abstract

The ‘systemic inflammatory response syndrome’ (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B4, thromboxane A2, and prostaglandin I2 were significantly lower in patients receiving EPA than in those not receiving it (all P < 0.01). Cytokines such as tumor necrosis factor-α, interferon-γ, and interleukin-10 were also significantly decreased by EPA (P < 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P < 0.05). The survival rate was significantly higher in the group given EPA (P < 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome. Bone Marrow Transplantation (2001) 28, 769–774.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 4
Figure 5
Figure 6
Figure 7
Figure 9
Figure 3
Figure 8

References

  1. Takatsuka H, Takemoto Y, Yamada S et al. Complications after bone marrow transplantation are manifestation of systemic inflammatory syndrome Bone Marrow Transplant 2000 26: 419–426

    Article  CAS  PubMed  Google Scholar 

  2. Endres S, Ghorbani R, Kelley VE et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acid on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells N Engl J Med 1989 320: 265–271

    Article  CAS  PubMed  Google Scholar 

  3. Chetty N, Vickers JD, Kinlough-Rathbone RL et al. Eicosapentaenoic acid interferes with U46619-stimulated formation of inositol phosphates in washed rabbit platelets Thromb Haemost 1989 62: 1116–1120

    Article  CAS  PubMed  Google Scholar 

  4. Chao NJ, Schmidt GM, Niland JC et al. Cyclosporin, methotrexate and prednisone compared with cyclosporin and prednisone for prophylaxis of acute graft-versus-host disease New Engl J Med 1993 329: 1225–1230

    Article  CAS  PubMed  Google Scholar 

  5. Singhal S, Mehta J, Powles R et al. Three weeks of ganciclovir for cytomegaloviraemia after allogeneic bone marrow transplantation Bone Marrow Transplant 1995 15: 777–781

    CAS  PubMed  Google Scholar 

  6. Obayashi T, Yoshida M, Mori T et al. Plasma (1→3)-β-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes Lancet 1995 345: 17–20

    Article  CAS  PubMed  Google Scholar 

  7. Przepiorka D, Weisdorf D, Martin P et al. 1994 Consensus conference on acute GVHD grading Bone Marrow Transplant 1995 15: 825–828

    CAS  PubMed  Google Scholar 

  8. Zeigler ZR, Shadduck RK, Nemunaitis J et al. Bone marrow transplant-associated thrombotic microangiopathy: a case series Bone Marrow Transplant 1995 15: 247–253

    CAS  PubMed  Google Scholar 

  9. Nunberger W, Michelmann I, Burdach S, Guel U . Endothelial dysfunction after bone marrow transplantation: increase of soluble thrombomodulin and PAI-1 in patients with multiple transplant-related complications Ann Hematol 1998 76: 61–65

    Article  Google Scholar 

  10. Takatsuka H, Takemoto Y, Okamoto T et al. Predicting the severity of graft-versus-host disease from interleukin-10 levels after bone marrow transplantation Bone Marrow Transplant 1999 24: 1005–1007

    Article  CAS  PubMed  Google Scholar 

  11. Takatsuka H, Takemoto Y, Okada M et al. Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: A case report Cytokine 2000 12: 1225–1227

    Article  CAS  PubMed  Google Scholar 

  12. Takatsuka H, Takemoto Y, Okamoto T et al. Thrombotic microangiopathy following allogeneic bone marrow transplantation Bone Marrow Transplant 1999 24: 303–306

    Article  CAS  PubMed  Google Scholar 

  13. Yamada S, Takatsuka H, Takemoto Y et al. Association of cytomegalovirus interstitial pneumonitis with HLA type following allogeneic bone marrow transplantation Bone Marrow Transplant 2000 25: 861–865

    Article  CAS  PubMed  Google Scholar 

  14. Takatsuka H, Takemoto Y, Okamoto T et al. Adult respiratory distress syndrome-like disorders after allogeneic bone marrow transplantation Transplantation 1999 68: 1343–1347

    Article  CAS  PubMed  Google Scholar 

  15. Takatsuka H, Takemoto Y, Okamoto T et al. The levels of soluble P-selectin, von Willebrand factor and thrombomodulin in patients with neurological complications after allogeneic bone marrow transplantation Bone Marrow Transplant 1998 21: 809–813

    Article  CAS  PubMed  Google Scholar 

  16. Chen X, Christou NV . Relative contribution of endothelial cell and polymorphonuclear neutrophil activation in their interactions in systemic inflammatory response syndrome Arch Surg 1996 131: 1148–1154

    Article  CAS  PubMed  Google Scholar 

  17. Members of the American College of Chest Physicians/Society of Critical Care Medicine ConsensusConference Committee: American college of chest physicians/society of critical care medicine consensus conference . Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis Crit Care Med 1922 20: 864–874

    Google Scholar 

  18. Kinsella JE, Lokesh B, Broughton S, Whelan J . Dietary polyunsaturated fatty acids and eicosanoids: potential effects on the modulation of inflammatory and immune cells: an overview Nutrition 1990 6: 24–44

    CAS  PubMed  Google Scholar 

  19. Terano T, Salmon JA, Moncada S . Biosynthesis and biological activity of leukotrien B5 Prostaglandins 1984 27: 217–232

    Article  CAS  PubMed  Google Scholar 

  20. Meydani SN, Endres S, Woods MM et al. Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women J Nutr 1991 121: 547–555

    Article  CAS  PubMed  Google Scholar 

  21. Fisher M, Upchurch KS, Levine PH et al. Effects of dietary fish oil supplementation on polymorphonuclear leukocyte inflammatory potential Inflammation 1986 10: 387–392

    Article  CAS  PubMed  Google Scholar 

  22. Schick PK, Menon S, Wojenski C . Effects of marine oil-enriched diets on guinea pig megakaryocyte and platelet lipids: effects on thromboxane synthesis and platelet function Biochim Biophys Acta 1990 1022: 49–56

    Article  CAS  PubMed  Google Scholar 

  23. Needleman P, Raz A, Minkes MS et al. Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties Proc Natl Acad Sci USA 1979 76: 944–948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tremoli E, Eligini S, Colli S et al. n-3 Fatty acid ethyl ester administration to healthy subjects and to hypertriglyceridemic patients reduces tissue factor activity in adherent monocytes Arterioscler Thromb 1994 14: 1600–1608

    Article  CAS  PubMed  Google Scholar 

  25. Harker LA, Kelly AB, Hanson SR et al. Interruption of vascular thrombus formation and vascular lesion formation by dietary n-3 fatty acids in fish oil in nonhuman primates Circulation 1993 87: 1017–1029

    Article  CAS  PubMed  Google Scholar 

  26. Shimokawa H, Vanhoutte PM . Dietary omega 3 fatty acids and endothelium-dependent relaxations in porcine coronary arteries Am J Physiol 1989 256: H968–973

    CAS  PubMed  Google Scholar 

  27. Okuda Y, Kawashima K, Sawada T et al. Eicosapentaenoic acid enhances nitric oxide production by cultured human endothelial cells Biochem Biophys Res Commun 1997 232: 487–491

    Article  CAS  PubMed  Google Scholar 

  28. Lawson DL, Mehta JL, Saldeen K et al. Omega-3 polyunsaturated fatty acids augment endothelium-dependent vasorelaxation by enhanced released of EDRF and vasodilator prostaglandins Eicosanoids 1991 4: 217–223

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank Ms A Utsumi and Ms Y Shikita for their expert technical assistance.

Author information

Authors and Affiliations

  1. Second Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    H Takatsuka, Y Takemoto, N Iwata, A Suehiro, T Hamano, T Okamoto & E Kakishita

  2. Third Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan

    A Kanamaru

Authors
  1. H Takatsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Takemoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Suehiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Hamano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Kanamaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E Kakishita
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Takatsuka, H., Takemoto, Y., Iwata, N. et al. Oral eicosapentaenoic acid for complications of bone marrow transplantation. Bone Marrow Transplant 28, 769–774 (2001). https://doi.org/10.1038/sj.bmt.1703226

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703226

Keywords

  • bone marrow transplantation
  • systemic inflammatory response syndrome
  • eicosapentaenoic acid
  • cytokine
  • endothelial damage

This article is cited by

Search

Advanced search

Quick links