Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1992;1(4):235–240. doi: 10.1155/S0962935192000358

Induction of circulating phospholipase A2 by intravenous administration of recombinant human tumour necrosis factor

Waldemar Pruzanski 1,✉, Matthew L Sherman 2, Donald W Kufe 2, Peter Vadas 1
PMCID: PMC2365345  PMID: 18475466

Abstract

We have examined the effects of intravenous infusion of recombinant human tumour necrosis factor (rh-TNF) on serum activity of phospholipase A2 (PLA2) in patients with malignancies. Nine patients received a 24 h continuous intravenous infusion ranging from 1.0 × 105 U/m2 to 3.0 × 105 U/m2; 14 patients received a 5 day continuous intravenous infusion ranging from 0.5 × 105 U/m2/day to 3.0 105 U/m2/day. Twenty one of 23 patients responded with marked increases in serum PLA2 activity that were detectable 3 h after the beginning of the rh-TNF infusion and reached maximum levels at 18 h with a mean increase of 16.2-fold. In patients receiving a 5 day rh-TNF infusion, the highest levels of PLA2 were observed after the first day of infusion. Serum PLA2 activity declined continuously to 2.9-fold above baseline at the end of the infusion. A significant correlation was noted between the dose of infused rh-TNF and the maximum increase in PLA2 activity. To our knowledge, this is the first time that an association between intravenous TNF administration and induction of circulating PLA2 in man has been established.

Full Text

The Full Text of this article is available as a PDF (493.8 KB).

Selected References

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

  1. Beutler B., Cerami A. The endogenous mediator of endotoxic shock. Clin Res. 1987 Apr;35(3):192–197. [PubMed] [Google Scholar]
  2. Brouckaert P., Spriggs D. R., Demetri G., Kufe D. W., Fiers W. Circulating interleukin 6 during a continuous infusion of tumor necrosis factor and interferon gamma. J Exp Med. 1989 Jun 1;169(6):2257–2262. doi: 10.1084/jem.169.6.2257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Demetri G. D., Spriggs D. R., Sherman M. L., Arthur K. A., Imamura K., Kufe D. W. A phase I trial of recombinant human tumor necrosis factor and interferon-gamma: effects of combination cytokine administration in vivo. J Clin Oncol. 1989 Oct;7(10):1545–1553. doi: 10.1200/JCO.1989.7.10.1545. [DOI] [PubMed] [Google Scholar]
  4. Edelson J. D., Vadas P., Villar J., Mullen J. B., Pruzanski W. Acute lung injury induced by phospholipase A2. Structural and functional changes. Am Rev Respir Dis. 1991 May;143(5 Pt 1):1102–1109. doi: 10.1164/ajrccm/143.5_Pt_1.1102. [DOI] [PubMed] [Google Scholar]
  5. Imamura K., Sherman M. L., Spriggs D., Kufe D. Effect of tumor necrosis factor on GTP binding and GTPase activity in HL-60 and L929 cells. J Biol Chem. 1988 Jul 25;263(21):10247–10253. [PubMed] [Google Scholar]
  6. Larrick J. W., Kunkel S. L. The role of tumor necrosis factor and interleukin 1 in the immunoinflammatory response. Pharm Res. 1988 Mar;5(3):129–139. doi: 10.1023/a:1015904721223. [DOI] [PubMed] [Google Scholar]
  7. Lefer A. M. Eicosanoids as mediators of ischemia and shock. Fed Proc. 1985 Feb;44(2):275–280. [PubMed] [Google Scholar]
  8. Michie H. R., Guillou P. J., Wilmore D. W. Tumour necrosis factor and bacterial sepsis. Br J Surg. 1989 Jul;76(7):670–671. doi: 10.1002/bjs.1800760706. [DOI] [PubMed] [Google Scholar]
  9. Michie H. R., Sherman M. L., Spriggs D. R., Rounds J., Christie M., Wilmore D. W. Chronic TNF infusion causes anorexia but not accelerated nitrogen loss. Ann Surg. 1989 Jan;209(1):19–24. doi: 10.1097/00000658-198901000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mohri M., Spriggs D. R., Kufe D. Effects of lipopolysaccharide on phospholipase A2 activity and tumor necrosis factor expression in HL-60 cells. J Immunol. 1990 Apr 1;144(7):2678–2682. [PubMed] [Google Scholar]
  11. Neale M. L., Fiera R. A., Matthews N. Involvement of phospholipase A2 activation in tumour cell killing by tumour necrosis factor. Immunology. 1988 May;64(1):81–85. [PMC free article] [PubMed] [Google Scholar]
  12. Palombella V. J., Vilcek J. Mitogenic and cytotoxic actions of tumor necrosis factor in BALB/c 3T3 cells. Role of phospholipase activation. J Biol Chem. 1989 Oct 25;264(30):18128–18136. [PubMed] [Google Scholar]
  13. Pruzanski W., Vadas P. Phospholipase A2--a mediator between proximal and distal effectors of inflammation. Immunol Today. 1991 May;12(5):143–146. doi: 10.1016/S0167-5699(05)80042-8. [DOI] [PubMed] [Google Scholar]
  14. Pruzanski W., Vadas P. Secretory synovial fluid phospholipase A2 and its role in the pathogenesis of inflammation in arthritis. J Rheumatol. 1988 Nov;15(11):1601–1603. [PubMed] [Google Scholar]
  15. Sherman M. L., Weber B. L., Datta R., Kufe D. W. Transcriptional and posttranscriptional regulation of macrophage-specific colony stimulating factor gene expression by tumor necrosis factor. Involvement of arachidonic acid metabolites. J Clin Invest. 1990 Feb;85(2):442–447. doi: 10.1172/JCI114457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Simpson S. Q., Casey L. C. Role of tumor necrosis factor in sepsis and acute lung injury. Crit Care Clin. 1989 Jan;5(1):27–47. [PubMed] [Google Scholar]
  17. Spriggs D. R., Sherman M. L., Imamura K., Mohri M., Rodriguez C., Robbins G., Kufe D. W. Phospholipase A2 activation and autoinduction of tumor necrosis factor gene expression by tumor necrosis factor. Cancer Res. 1990 Nov 15;50(22):7101–7107. [PubMed] [Google Scholar]
  18. Spriggs D. R., Sherman M. L., Michie H., Arthur K. A., Imamura K., Wilmore D., Frei E., 3rd, Kufe D. W. Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase I and pharmacologic study. J Natl Cancer Inst. 1988 Sep 7;80(13):1039–1044. doi: 10.1093/jnci/80.13.1039. [DOI] [PubMed] [Google Scholar]
  19. Suffys P., Beyaert R., Van Roy F., Fiers W. Reduced tumour necrosis factor-induced cytotoxicity by inhibitors of the arachidonic acid metabolism. Biochem Biophys Res Commun. 1987 Dec 16;149(2):735–743. doi: 10.1016/0006-291x(87)90429-3. [DOI] [PubMed] [Google Scholar]
  20. Tracey K. J., Lowry S. F., Cerami A. Cachectin: a hormone that triggers acute shock and chronic cachexia. J Infect Dis. 1988 Mar;157(3):413–420. doi: 10.1093/infdis/157.3.413. [DOI] [PubMed] [Google Scholar]
  21. Trang L. E. Prostaglandins and inflammation. Semin Arthritis Rheum. 1980 Feb;9(3):153–190. doi: 10.1016/0049-0172(80)90006-2. [DOI] [PubMed] [Google Scholar]
  22. Vadas P., Hay J. B. Involvement of circulating phospholipase A2 in the pathogenesis of the hemodynamic changes in endotoxin shock. Can J Physiol Pharmacol. 1983 Jun;61(6):561–566. doi: 10.1139/y83-086. [DOI] [PubMed] [Google Scholar]
  23. Vadas P., Pruzanski W., Kim J., Fornasier V. The proinflammatory effect of intra-articular injection of soluble human and venom phospholipase A2. Am J Pathol. 1989 Apr;134(4):807–811. [PMC free article] [PubMed] [Google Scholar]
  24. Vadas P., Pruzanski W., Stefanski E., Ellies L. G., Aubin J. E., Sos A., Melcher A. Extracellular phospholipase A2 secretion is a common effector pathway of interleukin-1 and tumour necrosis factor action. Immunol Lett. 1991 Jun;28(3):187–193. doi: 10.1016/0165-2478(91)90002-r. [DOI] [PubMed] [Google Scholar]
  25. Vadas P., Pruzanski W., Stefanski E., Ruse J., Farewell V., McLaughlin J., Bombardier C. Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study. J Lab Clin Med. 1988 May;111(5):584–590. [PubMed] [Google Scholar]
  26. Vadas P., Pruzanski W., Stefanski E., Sternby B. Compartmental heterogeneity of soluble phospholipases A. Inflammation. 1990 Apr;14(2):173–183. doi: 10.1007/BF00917456. [DOI] [PubMed] [Google Scholar]
  27. Vadas P., Pruzanski W., Stefanski E., Sternby B., Mustard R., Bohnen J., Fraser I., Farewell V., Bombardier C. Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A2 levels with circulatory collapse. Crit Care Med. 1988 Jan;16(1):1–7. doi: 10.1097/00003246-198801000-00001. [DOI] [PubMed] [Google Scholar]
  28. Vadas P., Wasi S., Movat H. Z., Hay J. B. Extracellular phospholipase A2 mediates inflammatory hyperaemia. Nature. 1981 Oct 15;293(5833):583–585. doi: 10.1038/293583a0. [DOI] [PubMed] [Google Scholar]
  29. Verheij H. M., Slotboom A. J., de Haas G. H. Structure and function of phospholipase A2. Rev Physiol Biochem Pharmacol. 1981;91:91–203. doi: 10.1007/3-540-10961-7_3. [DOI] [PubMed] [Google Scholar]
  30. Vishwanath B. S., Fawzy A. A., Franson R. C. Edema-inducing activity of phospholipase A2 purified from human synovial fluid and inhibition by aristolochic acid. Inflammation. 1988 Dec;12(6):549–561. doi: 10.1007/BF00914317. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES