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³¹P-Nuclear Magnetic Resonance Studies of the Effect of Recombinant Human Interleukin 1 on the Bioenergetics of RIF-1 Tumors¹

Johns Hopkins University, School of Medicine, Department of Radiology, Baltimore, Maryland 21205 [I. C., J. P. W., J. D. G.]; and the Laboratories of Experimental Therapeutics and Cell Biology, AMC Cancer Center, Denver, Colorado 80214 [P. G. B., N. K., C. S. J., P. F.]

The effect of a single injection of human recombinant interleukin 1 (IL-1) on s.c. RIF-1 tumors in mice was studied by in vivo ³¹P nuclear magnetic resonance spectroscopy. Spectra were obtained before and up to 24 h after IL-1. At 2, 4, 6, and 8 h after IL-1 injection, RIF-1 tumors exhibited a reduction in bioenergetic status compared to untreated controls. The P₁ to ß-nucleoside triphosphate and the phosphomonoester to ß-nucleoside triphosphate ratios increased, while the phosphocreatine to P₁ and phosphodiester to phosphomonoester ratios decreased. Tumor blood flow, estimated by ⁸⁶RbCl uptake, decreased within 30 min after IL-1 treatment. Minimum perfusion was detected at 4 h, with recovery between 6 and 12 h after IL-1 treatment. Histological sections of the RIF-1 tumors revealed intravascular congestion by 2 h, extravascular hemorrhage by 4 h, and necrosis by 12 h after treatment with IL-1. The time course of bioenergetic changes in RIF-1 tumors determined by ³¹P-NMR spectroscopy was found to parallel the reduction and subsequent recovery of tumor blood flow.

¹ This work has been supported in part by NIH Grants P01-CA44703, R01-CA48077, -CA33188 and a gift to AMC Cancer Research Center from The McDonnell Douglas Foundation.

² To whom requests for reprints should be addressed, at Department of Radiology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21205.

Received 6/14/89. Revised 8/16/89. Accepted 8/21/89.