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Steroid pretreatment reduces interleukin-2 toxicity in sheep
E D Morse1, R A Gunther, G J Jesmok
1Department of Surgery, University of California, Davis Medical Center, Sacramento 95817.
Surgery
|June 1, 1990
Summary
Steroids significantly reduced adverse cardiopulmonary effects from recombinant interleukin-2 (rIL-2) cancer therapy in sheep. This suggests steroids may mitigate rIL-2 toxicity by reducing inflammatory mediators.
Area of Science:
- Immunology
- Pharmacology
- Cardiopulmonary Physiology
Background:
- Recombinant interleukin-2 (rIL-2) shows promise for advanced cancer treatment.
- Therapeutic toxicity, particularly cardiopulmonary effects, limits rIL-2 use.
Purpose of the Study:
- To investigate the efficacy of steroids in mitigating adverse cardiopulmonary effects induced by rIL-2.
- To explore the potential mechanisms underlying rIL-2-induced toxicity.
Main Methods:
- Seven sheep underwent surgical preparation with vascular catheters and lung lymph fistulas.
- Sheep received either rIL-2 alone or rIL-2 with methylprednisolone pretreatment.
- Cardiopulmonary parameters and lung lymph flow were monitored.
Main Results:
- rIL-2 significantly increased lung lymph flow, cardiac output, heart rate, core temperature, and pulmonary artery pressure.
- Steroid pretreatment markedly attenuated the rIL-2-induced increase in lung lymph flow (40% vs. 140%).
- Adverse hemodynamic and respiratory changes associated with rIL-2 were prevented by steroid pretreatment.
Conclusions:
- Steroids effectively reduce the adverse cardiopulmonary effects of rIL-2 therapy.
- rIL-2-induced toxicity may involve arachidonic acid metabolism and inflammatory mediators.
- Steroid administration could be a viable strategy to improve rIL-2 tolerability in cancer patients.