Immunomodulatory effects of recombinant interleukin-3 treatment on human alveolar macrophages and monocytes.
The purpose of these studies was to examine the effects of in vivo and in vitro recombinant IL-3 treatment on alveolar macrophage and monocyte activities associated with antitumor and antimicrobial properties. Alveolar macrophages and blood monocytes from 6 patients receiving IL-3 (125-500 micrograms/m2/day) subcutaneously were isolated before therapy and at various times during the 15 days of therapy. Results indicated that tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6 (IL-6) secretion were enhanced from monocytes of all patients and from alveolar macrophages of patients receiving 500 micrograms/m2/day IL-3. Constitutive cytokine gene expression was present before therapy, but further enhancement was not detectable during therapy, suggesting a rapid time course of cytokine gene transcription and translation. Serum neopterin levels were elevated 2-5 fold in all patient compatible with the presence of augmented monocyte/macrophage activity. Peak levels of neopterin did not coincide with peak levels of cytokine secretion. In vitro studies of IL-3-treated normal alveolar macrophage and monocyte population demonstrated that IL-3 significantly augmented TNF and IL-6 secretion in monocytes, but not in alveolar macrophages. These differences in alveolar macrophage cytokine secretion observed after in vivo and in vitro IL-3 treatment may reflect the involvement of other cell populations in IL-3 modulation of alveolar macrophages in vivo. Monocytes, in contrast were comparably activated by IL-3 whether presented in vitro or in vivo.
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, Ohio 44195-5038.
M J
MJ
Thomassen
J M
JM
Antal
M J
MJ
Connors
D
D
McLain
K
K
Sandstrom
D P
DP
Meeker
G T
GT
Budd
D
D
Levitt
R M
RM
Bukowski
D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D019798:Neopterin; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019798:Neopterin