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Human recombinant interleukin-2 induces maturation and activation signals for feline eosinophils in vivo

Immunotherapy, with interleukin‐2 (IL‐2) or IL‐2 plus lymphokine‐activated killer (LAK) cells, has been used to treat cancer and acquired immunodeficiency syndrome (AIDS) in man. Similarities between feline leukemia virus (FeLV) infection in the cat and human immunodeficiency virus (HIV) infection i...

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Published in:Journal of leukocyte biology 1990-12, Vol.48 (6), p.531-540
Main Authors: Tompkins, Mary B., Novotney, Carol, Grindem, Carol B., Page, Rodney, English, Robert, Nelson, Philip, Tompkins, Wayne A.F.
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container_end_page 540
container_issue 6
container_start_page 531
container_title Journal of leukocyte biology
container_volume 48
creator Tompkins, Mary B.
Novotney, Carol
Grindem, Carol B.
Page, Rodney
English, Robert
Nelson, Philip
Tompkins, Wayne A.F.
description Immunotherapy, with interleukin‐2 (IL‐2) or IL‐2 plus lymphokine‐activated killer (LAK) cells, has been used to treat cancer and acquired immunodeficiency syndrome (AIDS) in man. Similarities between feline leukemia virus (FeLV) infection in the cat and human immunodeficiency virus (HIV) infection in man have prompted immunotherapeutic studies in the cat. To develop baseline data on hematological responses to infused IL‐2, cats were given daily (1–14 days) i.v. injections of 5 × 104 U/kg of recombinant human IL‐2 (rHulL‐2). Complete blood cell (CBC) counts were done weekly. Red blood cell (RBC), neutrophil, and lymphocyte numbers did not change appreciably over the course of the study. In contrast, rHulL‐2 caused an eosinophilia in all but the 1 day treatment group. Treatment for 3 days generated a transient eosinophilia on day 7 that returned to baseline by 3 weeks. Five day and 7 day treatments generated an eosinophilia by day 7 that peaked on day 14 and returned to normal values by day 28. Treatment of cats for 14 days did not increase the magnitude or duration of the eosinophilia beyond the 5 or 7 day treatments. Bone marrow (BM) biopsies from rHulL‐2‐treated cats revealed a marked selective hyperplasia of eosinophil precursors. In the 5 day treatment group, all maturation stages of eosinophils were elevated by week 1 of treatment. By week 2, the early stages had returned to normal, whereas the late stage cells remained elevated, suggesting an ordered maturation response. Numbers of all eosinophil precursors approximated pretreatment numbers by weeks 3–4. Thus the BM hyperplasia preceded the blood eosinophilia by 1 week, suggesting that an enhanced maturation response of BM eosinophil precursors is a major contributor to the rHulL‐2‐induced blood eosinophilia. In addition to a maturation signal, rHulL‐2 induces a potent activation signal for eosinophils as measured by a decrease in density and an increase in longevity in culture. The significance of the activated eosinophil in the therapeutic or toxicologic response to rHulL‐2 infusion is discussed.
doi_str_mv 10.1002/jlb.48.6.531
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Bone marrow (BM) biopsies from rHulL‐2‐treated cats revealed a marked selective hyperplasia of eosinophil precursors. In the 5 day treatment group, all maturation stages of eosinophils were elevated by week 1 of treatment. By week 2, the early stages had returned to normal, whereas the late stage cells remained elevated, suggesting an ordered maturation response. Numbers of all eosinophil precursors approximated pretreatment numbers by weeks 3–4. Thus the BM hyperplasia preceded the blood eosinophilia by 1 week, suggesting that an enhanced maturation response of BM eosinophil precursors is a major contributor to the rHulL‐2‐induced blood eosinophilia. In addition to a maturation signal, rHulL‐2 induces a potent activation signal for eosinophils as measured by a decrease in density and an increase in longevity in culture. The significance of the activated eosinophil in the therapeutic or toxicologic response to rHulL‐2 infusion is discussed.</abstract><cop>United States</cop><pub>Society for Leukocyte Biology</pub><pmid>2230598</pmid><doi>10.1002/jlb.48.6.531</doi><tpages>10</tpages></addata></record>
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identifier ISSN: 0741-5400
ispartof Journal of leukocyte biology, 1990-12, Vol.48 (6), p.531-540
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1938-3673
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subjects Animals
bone marrow
Bone Marrow Cells
Cats
Cell Survival - drug effects
Eosinophilia - chemically induced
Eosinophils - drug effects
Eosinophils - physiology
feline leukemia virus
Female
Hematopoietic Stem Cells - drug effects
Humans
Interleukin-2 - pharmacology
Killer Cells, Lymphokine-Activated - drug effects
Leukocyte Count
Male
Recombinant Proteins - pharmacology
Time Factors
white blood cells
title Human recombinant interleukin-2 induces maturation and activation signals for feline eosinophils in vivo
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