Selective induction of interleukin-1 receptor antagonist and interleukin-8 in human monocytes by normal polyspecific IgG (intravenous immunoglobulin).
We have investigated the effects of intravenous immunoglobulin (IVIg), a therapeutic preparation of normal human polyspecific IgG, on the synthesis and release of cytokines by peripheral blood monocytes. IVIg was found to selectively induce gene transcription and secretion of interleukin-1 receptor antagonist (IL-1ra) and IL-8 in cultures of normal human monocytes. The addition of IVIg to cultures of purified monocytes induced a dose-dependent secretion of IL-1ra and IL-8 without stimulating the production of IL-1 alpha, IL-1 beta, tumor necrosis factor-alpha or IL-6. The effects of IVIg required both the Fc and F(ab')2 portions of IgG. IVIg-induced production of IL-8 by monocytes was enhanced by lipopolysaccharide (LPS), although LPS inhibited the secretion of IL-1ra, suggesting that IVIg and LPS stimulate distinct intracellular pathways in monocytes. Induction of IL-1ra and IL-8 by IVIg was enhanced in the presence of autologous T lymphocytes. Our observations document the selectivity of the effects of IVIg on the synthesis of cytokines and cytokine antagonists by human monocytes. Induction of IL-1ra and IL-8 by IVIg may contribute to the anti-inflammatory effects of immunoglobulin therapy in patients with autoimmune and systemic inflammatory disorders.
Ruiz de Souza
V
V
INSERM U430, Hôpital Broussais, Paris, France.
Carreno
M P
MP
Kaveri
S V
SV
Ledur
A
A
Sadeghi
H
H
Cavaillon
J M
JM
Kazatchkine
M D
MD
Haeffner-Cavaillon
N
N
D002450:Cell Communication; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; C507763:IL1RN protein, human; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D016756:Immunoglobulins, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012795:Sialoglycoproteins