Antitumor Effects of Recombinant Human Interleukin La in RIF-1 and PANC02 Solid Tumors

Paul G. Braunschweiger, Candace S. Johnson, Nirmal Kumar, Virginia Ord, Philip Furmanski

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69 Scopus citations

Abstract

The antitumor effects of recombinant human interleukin 1α (IL-1) were determined in RIF-1 and Panc02 murine solid tumors. Acute tumor hemorrhage was observed in both models as early as 3 h after a single 25 μg/kg IL-1 treatment and was quantitated by the intratumor accumulation of 59Fe-labeled erythrocytes (RBC). The IL-1-mediated hemorrhagic response was maximal 6-12 h after treatment and greater in Panc02 tumors than in RIF-1 tumors. Hemorrhagic responses to RIF-1 tumors growing in athymic nude mice were similar to those seen for RIF-1 tumors in C3H/HeJ mice. This acute vascular injury was accompanied by progressive edema in tumors but not in skin or muscle. In RIF-1 tumors, the extracell water volume at 12 h after IL-1 (395 μl/g) was nearly twice that in untreated controls (215 μl/g). IL-1 also produced marked reductions in tumor blood flow as early as 1 h after treatment. Maximal blood flow restriction was seen at 6 h after IL-1. Although restricted bood flow was observed in tumors for up to 48 h, IL-1 effects on muscle, liver, and skin blood flow were transient with recovery by 12 h after treatment. IL-1 (up to 0.4 ng/ml for 72 h) was not toxic to RIF-1 tissue culture cells in vitro, but 0.2 ng/ml IL-1, for 20 h, reduced the clonogenicity of RIF-1 cells in primary explant cultures by approximately 50%. In vivo, the clonogenic cellularity of RIF-1 tumors was reduced by 70%, 24 h after a single 25 μg/kg treatment. Increased clonogenic cell proliferation was observed at 24 h, and rapid repopulation of the clonogenic cell population was seen by 48 h. Although IL-1 transiently slowed the growth of RIF-1 tumors, no significant regrowth delay was observed. In Panc02 tumors, cell proliferation was also inhibited after IL-1. Recovery, however, was delayed and occurred more slowly than in RIF-1 tumors. Significant growth inhibition and regrowth delay (5 days) was observed in Panc02 tumors after a single IL-1 treatment. The results of these studies show that IL-1 has significant effects on the pathophysiology of both RIF-1 and Panc02 tumors in vivo. Further, our results indicate that these effects may be mediated through the activation of a non T-cell, adherent cell population residing in the tumor at the time of IL-1 treatment.

Original languageEnglish (US)
Pages (from-to)6011-6016
Number of pages6
JournalCancer Research
Volume48
Issue number21
StatePublished - Nov 1988

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Braunschweiger, P. G., Johnson, C. S., Kumar, N., Ord, V., & Furmanski, P. (1988). Antitumor Effects of Recombinant Human Interleukin La in RIF-1 and PANC02 Solid Tumors. Cancer Research, 48(21), 6011-6016.