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Increased circulating nitrogen oxides after human tumor immunotherapy: correlation with toxic hemodynamic changes.

J B Ochoa¹, B Curti, A B Peitzman

¹Department of Surgery, University of Pittsburgh, PA 15261.

Journal of the National Cancer Institute

|June 3, 1992

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Interleukin-2 (IL-2) cancer therapy can cause hypotension due to increased nitric oxide (NO) production. This study found higher nitrate levels and lower blood pressure in patients undergoing IL-2 treatment, suggesting NO mediates these toxic effects.

Area of Science:

Immunology
Pharmacology
Cardiovascular Physiology

Background:

Interleukin-2 (IL-2) immunotherapy can cause vascular leak syndrome, hypotension, and low systemic vascular resistance.
Nitric oxide (NO), a mediator of vascular smooth muscle relaxation, is produced by cells exposed to inflammatory cytokines.

Purpose of the Study:

To determine if NO production increases in patients receiving IL-2 immunotherapy.
To correlate increased NO production with hemodynamic instability during IL-2 treatment.

Main Methods:

Studied 12 patients undergoing IL-2 and T-AK cell immunotherapy.
Measured plasma nitrate (NO3-), the stable metabolite of NO, before and after IL-2 treatment cycles.

Main Results:

Related Experiment Videos

Observed a ninefold increase in plasma NO3- levels after 7 days of IL-2 treatment (P < .0001).
All patients experienced significant decreases in systolic and diastolic blood pressure (P < .001).

Conclusions:

Propose that IL-2 induces NO synthase, leading to increased NO production and clinically significant hypotension.
Suggest L-arginine analogues could competitively inhibit NO synthesis, potentially managing toxic side effects of IL-2 cancer therapies.