Journal of Clinical Immunology

, Volume 9, Issue 2, pp 169–173 | Cite as

Appearance of neuropeptides in ascitic fluid after peritoneal therapy with interleukin-2 and lymphokine-activated killer cells for intraabdominal malignancy

  • Simion A. Schiogolev
  • Edward J. Goetzl
  • Walter J. Urba
  • Dan L. Longo
Original Articles


Administration of intravenous interleukin-2 (IL-2), followed by intraperitoneal IL-2 and autologous lymphokine-activated killer (LAK) cells to six patients with colonic, ovarian, or endometrial carcinoma restricted to peritoneal spread increased significantly the ascitic fluid concentrations of the neuropeptides substance P (SP) and calcitonin-gene related peptide (CGRP). After intravenous IL-2 alone, the level of SP rose 10- to 140-fold, without a change in that of CGRP. Intraperitoneal IL-2 and LAK cells led to elevations in the concentrations of SP and CGRP to respective maximal means of 319 and 175 pM after 8 hr, which were maintained for 24–48 hr without alterations in the levels of vasoactive intestinal peptide or somatostatin. SP and CGRP from peritoneal fluid were chromatographically indistinguishable from synthetic neuropeptides. The increases in concentrations of SP and CGRP after IL-2 and LAK-cell therapy are the first demonstration of a neural response to a human cellular immunological reaction. The time course and magnitude of the neuropeptide response suggest a role in the vascular side effects of this form of treatment.

Key words

Interleukin-2 lymphokine-activated killer (LAK) cells neuropeptides mediators cancer 


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  1. 1.
    Papa MZ, Mule JJ, Rosenerg SA: Antitumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: Successful immunotherapy of established pulmonary metastases from weakly immunogenic and nonimmunogenic murine tumors of three distinct histological types. Cancer Res 46:4973–4978, 1986Google Scholar
  2. 2.
    Lafreniere R, Rosenberg, SA: Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (RIL 2) can mediate the regression of both immunogenic and nonimmunogenic sarcomas and an adenocarcinoma. J Immunol 135:4273–4280, 1985Google Scholar
  3. 3.
    Mule JJ, Shu S, Rosenberg SA: The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo. J Immunol 135:646–652, 1985Google Scholar
  4. 4.
    Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp C, Simpson C, Reichert CM: Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1492, 1985Google Scholar
  5. 5.
    Lotze MT, Chang AE, Seipp CA, Simpson C, Vetto JT, Rosenberg SA: High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer: Responses, treatment-related morbidity, and histologic findings. JAMA 256:3117–3124, 1986Google Scholar
  6. 6.
    Lotze MT, Custer MC, Rosenberg SA: Intraperitoneal administration of interleukin 2 in patients with cancer. Arch Surg 121:1373–1379, 1986Google Scholar
  7. 7.
    Steis R, Bookman M, Clark J, Urba W, McKnight J, Smith J, Schoenberger C, Ozols R, Young R, Maluish A, Beckner S, Longo D: Intraperitoneal lymphokine activated killer (LAK) cell and interleukin 2 (IL 2) therapy for peritoneal carcinomatosis: Toxicity, efficacy, and laboratory results. Proc Am Soc Clin Oncol 6:250, 1987Google Scholar
  8. 8.
    Walker KB, Serwonska MH, Valone, FH, Harkonen WS, Frick OL, Scriven KH, Ratnoff WD, Browning JG, Payan DG and Goetzl EJ: Distinctive patterns of release of neuroendocrine peptides after nasal challenge of allergic subjects with ryegrass antigen. J Clin Immunol 8:108–113, 1988Google Scholar
  9. 9.
    Aliakbari J, Sreedharan SP, Turck CW, Goetzl EJ: Selective localization of vasoactive intestinal peptide and substance P in human eosinophils. Biochem Biophys Res Commun 148:1440–1445, 1987Google Scholar
  10. 10.
    Barnes PJ: Airway neuropeptides and asthma. Trend Pharm Sci 8:24–27, 1987Google Scholar
  11. 11.
    Brain SD, Tippins JR, Morris HR, MacIntyre I, Williams TJ: Potent vasodilator activity of calcitonin gene-related peptide in human skin. J Invest Dermatol 87:533–536, 1986Google Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Simion A. Schiogolev
    • 1
  • Edward J. Goetzl
    • 1
  • Walter J. Urba
    • 2
  • Dan L. Longo
    • 2
  1. 1.Howard Hughes Medical Institute and Department of MedicineUniversity of California Medical CenterSan Francisco
  2. 2.Program Resources, Inc., and Biological Response Modifiers ProgramNational Cancer Institute, Frederick Cancer Research FacilityFrederick

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