Endocrine effects of IL-1α and β administered in a phase i trial to patients with advanced cancer

Brendan D. Curti, Walter J. Urba, Dan L. Longo, John Edward Janik, William H. Sharfman, Langdon L. Miller, Giovanni Cizza, Masanao Shimizu, Joost J. Oppenheim, W. Gregory Alvord, John W. Smith

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Previous primate and rodent studies suggested that interleukin-1α (IL-1α) caused changes in the secretion of pituitary, adrenal, thyroid, and gonadal hormones, as well as acute-phase reactants. Plasma samples were obtained after IL-1α and β treatment in cancer patients to document the changes in endocrine function suggested by the animal models. Successive groups of patients were treated at IL-1α doses of 0.01, 0.03, 0.1, 0.3, and 1.0 µg/kg, given daily as a 15-min intravenous bolus. IL-1β was given at 0.1 µg/kg by the same route and time course. After the first dose of IL-1, statistically significant elevations of a.m. and p.m. cortisol, growth hormone (GH), and prolactin (PRL) occurred. Thyroid-stimulating hormone (TSH) and C-reactive protein (CRP) were elevated by the sixth treatment day. Testosterone decreased significantly in male patients. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were more variable but decreased in most patients. The changes in cortisol, GH, PRL, TSH, CRP, FSH, LH, and testosterone resolved after treatment and did not result in clinically apparent endocrinopathies. Bolus doses of IL-1α and β cause significant changes in many endocrine laboratory parameters and influence the in vivo activities of multiple homeostatic endocrine functions in human beings.

Original languageEnglish (US)
Pages (from-to)142-148
Number of pages7
JournalJournal of Immunotherapy
Volume19
Issue number2
DOIs
StatePublished - 1996

Keywords

  • Cortisol
  • Interleukin-1
  • Pituitary hormones
  • Testosterone

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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