Decrease in Interleukin 2-induced Vascular Leakage in the Lungs of Mice by Administration of Recombinant Interleukin 1α in Vivo

Rai K. Puri, William D. Travis, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

The administration of interleukin 2 (IL-2) to mice and humans is limited by the induction of a dose-dependent increase in vascular permeability causing a vascular leak syndrome (VLS). We have investigated the impact of the injection of recombinant interleukin la (IL-la) on the VLS induced by IL-2 by measuring the extravasation of 125I-albuinin into tissues and by assessing wet and dry lung weights. IL-lα alone did not induce any significant extravasation of radiolalbeled albumin. IL-2 alone, however, caused a significant increase in the extravasadon compared to control lungs. IL-lα injection along with IL-2 significantly reduced the IL-2-induced extravasation of radiolabeled albumin [9,886 ± 533 (SEM) cpm were observed in IL-2 and IL-lα-treated lungs compared to 14,172 ± 2,628 cpm in lungs treated with IL-2 alone (P < 0.02)]. IFN-α in combination with IL-2 produced more severe vascular leakage than caused by IL-2 alone. IL-lα also significantly decreased (P < 0.05) the vascular permeability induced by the combination of IFN-α and IL-2. We observed 44,811 ± 13,131 cpm in IFN-α and IL-2-treated lungs compared to 18,350 ± 2,622 cpm in IFN-α-IL-2-and IL-lα-treated lungs. The IL-2 and IFN-α-induced increase in lung water weight was also reduced significantly by the addition of IL-lα. The decrease in vascular leakage was dependent on the dose and timing of IL-la administered. When recombinant IL-la was given as a single i.p. injection, 24 h before the injection of IL-2 (or Hanks' balanced salt solution) or IL-2 and IFN-α no abrogation of the VLS was observed. Although IL-lα decreased VLS significantly in mice treated with IFN-α and IL-2 the survival of mice was not improved by the simultaneous administration of IL-lα. Histologically, treatment with IFN-α and IL-2 produced marked perivascular and intraalveolar edema which was completely eliminated by the addition of IL-lα. However, some perivascular edema in IL-lα-treated mice remained which was equivalent to that caused by IL-2 alone. Treatment of MCA-106 induced pulmonary metastases was enhanced by the administration of IFN-α and IL-2 together. IL-lα did not abrogate the therapeutic efficacy of this combination despite the ability of IL-la to decrease the VLS. Our results indicate that the administration of IL-la decreased the VLS in the lungs of mice treated with IL-2 or IL-2 plus IFN-α. This observation may have clinical relevance to the treatment of patients with IL-2 or combination of IL-2 with other lymphokines.

Original languageEnglish (US)
Pages (from-to)969-976
Number of pages8
JournalCancer Research
Volume49
Issue number4
StatePublished - Feb 15 1989

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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