Histamine release from basophils after in vivo application of recombinant human interleukin-3 in man.
Interleukin 3 (IL3) is known to stimulate progenitor cell proliferation and maturation as well as differentiated cell functions, e.g. direct or anti-IgE-mediated histamine release (HR). We investigated 14 patients with malignant diseases being treated with recombinant human IL3 (rhuIL3) as a daily subcutaneous bolus injection for 15 days. For analysis, patients were combined in a 'low-dose' [30 (n = 1), 60 (n = 3) and 125 (n = 2) micrograms/m2/day] and a 'high-dose' [250 (n = 6) and 500 (n = 2) micrograms/m2/day] therapy group. In the high-dose group there was a 2-fold increase in total leukocytes, and 8-fold increase in basophils, and a 23-fold increase in eosinophils. Histamine content per basophil decreased rapidly after rhuIL3 administration. Anti-IgE-induced HR increased in a dose-dependent manner after rhuIL3 therapy (low-dose group: HRmax 47.5 vs. 53.3%; high-dose group: HRmax 57.8 vs. 75.4%, p less than 0.05). In contrast to anti-IgE-induced HR, HR with ionophore (78.0 vs. 50.3%, p less than 0.05), FMLP (32.3 vs. 11.4%, p less than 0.05), sodium chloride (31.8 vs. 22.6%, n.s.) and mannitol (56.3 vs. 47.8%, n.s.) decreased. There was no histamine release from basophils upon in vitro stimulation with rhuIL3 alone. The kinetics of the increase in anti-IgE-induced histamine release did not parallel the rapid histamine depletion of cells. We conclude that rhuIL3 therapy may cause a rapid HR from basophils which cannot be observed after stimulation of cells in vitro. The clinical importance of this HR remains unclear as side effects could not be correlated with HR.(ABSTRACT TRUNCATED AT 250 WORDS)
Merget
R D
RD
Department of Pneumology, University Hospital, Johann Wolfgang Goethe University, Frankfurt/Main, FRG.
Maurer
A B
AB
Koch
U
U
Ganser
A
A
Ottmann
O G
OG
Schultze-Werninghaus
G
G
Seipelt
G
G
Zachgo
W
W
Hoelzer
D
D
Meier-Sydow
J
J
D000368:Aged; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007377:Interleukin-3 / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology
D007377:Interleukin-3; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine