Document Detail


Steroid pretreatment reduces interleukin-2 toxicity in sheep.
MedLine Citation:
PMID:  2353306     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recombinant interleukin-2 (rIL-2) has shown promise in the treatment of patients with advanced cancer. However, toxicity of this therapy remains a major problem with its use in some patients. In this study we examined whether steroids could reduce the adverse cardiopulmonary effects of rIL-2. Seven sheep were surgically prepared with vascular catheters and lung lymph fistulas. Each sheep received either a single dose of rIL-2 (100 micrograms/kg) or rIL-2 plus methylprednisolone (30 mg/kg) followed by the reverse treatment 1 week later. Lung lymph flow increased markedly after rIL-2 with a peak QL of 140% +/- 30% (above baseline). Steroid pretreatment significantly reduced this lymph flow increase with peak lung lymph flow being only 40% +/- 16% (p less than 0.004). The lymph/plasma protein ratio tended to increase after rIL-2, but these changes were not statistically significant. After rIL-2, cardiac output, heart rate, core temperature, and mean pulmonary artery pressure increased (p less than 0.05), whereas systemic vascular resistance and arterial PO2 decreased (p less than 0.05). These changes did not occur with steroid pretreatment. The results of this study demonstrate that steroids reduced the adverse cardiopulmonary effects of rIL-2. We believe that rIL-2 induces activation of arachidonic acid metabolism, which leads to the production of multiple inflammatory mediators that cause increased microvascular permeability and the adverse cardiopulmonary effects of rIL-2.
Authors:
E D Morse; R A Gunther; G J Jesmok; K S Hughes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Surgery     Volume:  107     ISSN:  0039-6060     ISO Abbreviation:  Surgery     Publication Date:  1990 Jun 
Date Detail:
Created Date:  1990-07-13     Completed Date:  1990-07-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  639-47     Citation Subset:  AIM; IM    
Affiliation:
Department of Surgery, University of California, Davis Medical Center, Sacramento 95817.
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Gases / blood
Hemodynamics / drug effects
Interleukin-2 / poisoning*
Leukocyte Count / drug effects
Lung / physiology
Lymph / physiology
Methylprednisolone / pharmacology*
Pulmonary Circulation
Sheep
Chemical
Reg. No./Substance:
0/Gases; 0/Interleukin-2; 83-43-2/Methylprednisolone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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