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. 1994 Mar;69(3):596–598. doi: 10.1038/bjc.1994.109

A pilot study to evaluate the effects of C1 esterase inhibitor on the toxicity of high-dose interleukin 2.

A C Ogilvie 1, J W Baars 1, A J Eerenberg 1, C E Hack 1, H M Pinedo 1, L G Thijs 1, J Wagstaff 1
PMCID: PMC1968861  PMID: 8123494

Abstract

In a pilot study six patients received 4 days' treatment with interleukin 2 (IL-2) [cumulative dose (CD) 264 +/- 26 x 10(6) IU m-2] and C1 esterase inhibitor (C1-INH) (loading dose 2,000 U, followed by 500-1,000 U twice daily). Toxicity was compared with that in patients given 4 days' treatment with standard (CD 66 +/- 12 x 10(6) IU m-2) or escalating-dose (CD 99 +/- 8 x 10(6) IU m-2) IL-2. IL-2-induced hypotension was equivalent and complement activation was less after IL-2 + C1-INH (C3a = 10.5 +/- 3.2 nmol l-1) than following standard (14.1 +/- 8.4 nmol l-1) or escalating-dose (18.3 +/- 2.9 nmol l-1) IL-2. This study demonstrates that C1-INH administration during IL-2 treatment is safe and warrants further study to evaluate its ability to ameliorate IL-2-induced toxicity.

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Selected References

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

  1. Baars J. W., Hack C. E., Wagstaff J., Eerenberg-Belmer A. J., Wolbink G. J., Thijs L. G., Strack van Schijndel R. J., van der Vall H. L., Pinedo H. M. The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2. Br J Cancer. 1992 Jan;65(1):96–101. doi: 10.1038/bjc.1992.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clayman G. L., Liu F. J., Savage H. E., Taylor D. L., Lavedan P., Buchsbaum R. M., Pellegrino C., Trujillo J. M., Young G., Schantz S. P. Acute-phase proteins in patients with head and neck cancer treated with interleukin 2/interferon alfa. Arch Otolaryngol Head Neck Surg. 1992 Jan;118(1):41–48. doi: 10.1001/archotol.1992.01880010045014. [DOI] [PubMed] [Google Scholar]
  3. Hack C. E., Paardekooper J., Eerenberg A. J., Navis G. O., Nijsten M. W., Thijs L. G., Nuijens J. H. A modified competitive inhibition radioimmunoassay for the detection of C3a. Use of 125I-C3 instead of 125I-C3a. J Immunol Methods. 1988 Apr 6;108(1-2):77–84. doi: 10.1016/0022-1759(88)90405-x. [DOI] [PubMed] [Google Scholar]
  4. Hack C. E., Voerman H. J., Eisele B., Keinecke H. O., Nuijens J. H., Eerenberg A. J., Ogilvie A., Strack van Schijndel R. J., Delvos U., Thijs L. G. C1-esterase inhibitor substitution in sepsis. Lancet. 1992 Feb 8;339(8789):378–378. doi: 10.1016/0140-6736(92)91705-d. [DOI] [PubMed] [Google Scholar]
  5. Mier J. W., Vachino G., Klempner M. S., Aronson F. R., Noring R., Smith S., Brandon E. P., Laird W., Atkins M. B. Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2-associated side effects. Blood. 1990 Nov 15;76(10):1933–1940. [PubMed] [Google Scholar]
  6. Moore F. D., Jr, Schoof D. D., Rodrick M., Eberlein T. J. The systemic complement activation caused by interleukin-2/lymphokine-activated killer-cell therapy of cancer causes minimal systemic neutrophil activation. Int J Cancer. 1991 Oct 21;49(4):504–508. doi: 10.1002/ijc.2910490405. [DOI] [PubMed] [Google Scholar]
  7. Nuijens J. H., Eerenberg-Belmer A. J., Huijbregts C. C., Schreuder W. O., Felt-Bersma R. J., Abbink J. J., Thijs L. G., Hack C. E. Proteolytic inactivation of plasma C1- inhibitor in sepsis. J Clin Invest. 1989 Aug;84(2):443–450. doi: 10.1172/JCI114185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Thijs L. G., Hack C. E., Strack van Schijndel R. J., Nuijens J. H., Wolbink G. J., Eerenberg-Belmer A. J., Van der Vall H., Wagstaff J. Activation of the complement system during immunotherapy with recombinant IL-2. Relation to the development of side effects. J Immunol. 1990 Mar 15;144(6):2419–2424. [PubMed] [Google Scholar]
  9. Vachino G., Gelfand J. A., Atkins M. B., Tamerius J. D., Demchak P., Mier J. W. Complement activation in cancer patients undergoing immunotherapy with interleukin-2 (IL-2): binding of complement and C-reactive protein by IL-2-activated lymphocytes. Blood. 1991 Nov 15;78(10):2505–2513. [PubMed] [Google Scholar]
  10. Vetto J. T., Papa M. Z., Lotze M. T., Chang A. E., Rosenberg S. A. Reduction of toxicity of interleukin-2 and lymphokine-activated killer cells in humans by the administration of corticosteroids. J Clin Oncol. 1987 Mar;5(3):496–503. doi: 10.1200/JCO.1987.5.3.496. [DOI] [PubMed] [Google Scholar]

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