Chest
Volume 94, Issue 4, October 1988, Pages 750-754
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Interleukin-2 Administration Causes Reversible Hemodynamic Changes and Left Ventricular Dysfunction Similar to Those Seen in Septic Shock

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Interleukin-2, a lymphocyte product, has well demonstrated antitumor activity in humans. Early clinical studies showed hemodynamic alterations in patients receiving the drug as antitumor immunotherapy. We serially assessed interleukin-2-associated hemodynamic parameters and left ventricular ejection fractions in five patients with neoplastic diseases unresponsive to conventional therapies. By day 4 of therapy, compared with baseline (preinterleukin-2), all patients developed tachycardia (p<0.01), decreased mean arterial blood pressure (p<0.05), increased cardiac index (p<0.05), and decreased systemic vascular resistance (p<0.01). In addition, left ventricular ejection fraction fell from 58.0 ± 4.7 to 36.4 ± 4.0 percent (0.05<p<0.10), which was associated with a trend toward left ventricular dilatation manifested by an increase in left ventricular end-diastolic volume index. Transient renal dysfunction was noted in all five patients, and one developed transient respiratory failure; both types of organ dysfunction recovered to baseline values after cessation of immunotherapy. Thus, interleukin-2 induces multiple reversible cardiovascular abnormalities that are similar to the hemodynamic manifestations of human septic shock. (Chest 1988; 94:750-54)

Section snippets

Patients

Patients with tumors unresponsive to conventional therapy were admitted to the medical intensive care unit at the National Institutes of Health before the administration of interleukin-2, with or without the addition of lymphokine-activated killer (LAK) cells. All patients had consented to therapy with interleukin-2, and additional informed consent was obtained from each patient before any invasive hemodynamic monitoring.

Hemodynamic Monitoring

Heart rate (HR) was monitored using Hewlett-Packard ECG equipment.

Patients

In this study, five patients received high-dose (100,000 units/kg) interleukin-2, and four of these five patients also received LAK cells as antineoplastic immunotherapy for a duration of at least four days. Clinical data are summarized in Table 1. The underlying diseases were renal cell carcinoma (2), malignant melanoma (1), rhabdomyosarcoma (1), and widespread Kaposi's sarcoma due to the acquired immunodeficiency syndrome (1). None of these patients had received doxorubicin or other

DISCUSSION

Interleukin-2 administration was associated with a hemodynamic pattern that is similar to the hemodynamic changes seen in septic shock. These alterations, which occurred within 24 hours of interleukin-2 administration, included profound tachycardia, decreased mean arterial blood pressure, increased cardiac index, decreased systemic vascular resistance, and decreased left ventricular stroke work index. All of these hemodynamic changes have been well described in human septic shock.12, 13, 14, 15

ACKNOWLEDGMENTS

The authors thank the nursing and technical staffs of the Medical Intensive Care Unit, NIH, for their assistance in patient care and data collection during the administration of interleukin-2; the nurses from the Department of Nuclear Medicine for performing the radionuclide studies; and Kathy Kiefer and Shelia Robinson for preparation of the manuscript.

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Presented in part at the annual meeting, American Federation for Clinical Research, May 1986, and at the Annual Symposium of Critical Care Medicine, May 1986. Published in abstract form in Clinical Research 1986; 34:413A, and in Critical Care Medicine 1986; 14:352.

Manuscript received January 5; revision accepted March 22.

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