Administration of intravenous immunoglobulin (IVIG) in vivo—down‐regulatory effects on the IL‐1 system

Modulation of the cytokine network may be of importance for the beneficial effects of therapy with IVIG seen in a wide range of immune‐mediated disorders. In the present study we investigate the effect of IVIG administration in vivo on the IL‐1 system in 12 patients with primary hypogammaglobulinaemia. Before IVIG infusion these patients had significantly elevated levels of IL‐1α and IL‐1β both in plasma and in supernatants from peripheral blood mononuclear cells (PBMC) compared with healthy controls. After one bolus infusion with IVIG (0.4 g/kg) we found a significant change in the profile of the components of the IL‐1 system: a marked increase in levels of IL‐1 receptor antagonist (IL‐1Ra) and neutralizing antibodies against IL‐1α, a moderate decrease in levels of IL‐1α, IL‐1β and soluble (s) IL‐1 receptor type I and a significant increase in sIL‐1 receptor type II levels. These changes were found both in plasma and in PBMC isolated after IVIG administration. Furthermore, pooled serum obtained after IVIG infusion suppressed lipopolysaccharide‐ and staphylococcal enterotoxin B‐stimulated, but not phorbol myristate acetate‐stimulated, release of IL‐1α and IL‐1β from PBMC isolated from healthy controls. Finally, these changes in circulating levels of various IL‐1 modulators after IVIG infusion appeared to cause a significantly impaired ability of IL‐1 to stimulate PBMC for tumour necrosis factor‐alpha release. Our findings suggest that IVIG administration may not only down‐regulate the activity in the IL‐1 system, but also hamper IL‐1 stimulation of PBMC.

[1]  K. Bendtzen,et al.  High-avidity autoantibodies to cytokines. , 1998, Immunology today.

[2]  S. Frøland,et al.  Effects of intravenous immunoglobulin in vivo on abnormally increased tumor necrosis factor-alpha activity in human immunodeficiency virus type 1 infection. , 1997, The Journal of infectious diseases.

[3]  K. Bendtzen,et al.  Increased In Vivo Antibody Activity Against Interferon α, Interleukin-1α, and Interleukin-6 After High-Dose Ig Therapy , 1997 .

[4]  M. Ballow.  Mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory diseases. , 1997, The Journal of allergy and clinical immunology.

[5]  J. Farrant,et al.  Common variable immunodeficiency: how many diseases? , 1997, Immunology today.

[6]  M. Dalakas.  Intravenous Immune Globulin Therapy for Neurologic Diseases , 1997, Annals of Internal Medicine.

[7]  M. Eibl,et al.  Immunomodulatory effect of immunoglobulins. , 1996, Clinical and experimental rheumatology.

[8]  R. Kaul,et al.  Plasma from patients with severe invasive group A streptococcal infections treated with normal polyspecific IgG inhibits streptococcal superantigen-induced T cell proliferation and cytokine production. , 1996, Journal of immunology.

[9]  C. Dinarello,et al.  Biologic basis for interleukin-1 in disease. , 1996, Blood.

[10]  S. Frøland,et al.  Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency--possible immunologic and clinical consequences. , 1996, Blood.

[11]  W. Arend,et al.  Differential binding of human interleukin‐1 (IL‐1) receptor antagonist to natural and recombinant soluble and cellular IL‐1 type I receptors , 1995, European journal of immunology.

[12]  R. Berge,et al.  Decreased levels of total and reduced glutathione in CD4+ lymphocytes in common variable immunodeficiency are associated with activation of the tumor necrosis factor system: possible immunopathogenic role of oxidative stress. , 1995, Blood.

[13]  Smiley Jd,et al.  Southwestern Internal Medicine Conference: high-dose intravenous gamma globulin therapy: how does it work? , 1995 .

[14]  J. Cavaillon,et al.  Selective induction of interleukin‐1 receptor antagonist and interleukin‐8 in human monocytes by normal polyspecific IgG (intravenous immunoglobulin) , 1995, European journal of immunology.

[15]  A. Ahmed,et al.  Intravenous immunoglobulins in the therapy of autoimmune and systemic inflammatory disorders. , 1995, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[16]  S. Dower,et al.  Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses. , 1994, Journal of immunology.

[17]  K. Bendtzen.  Cytokines and natural regulators of cytokines. , 1994, Immunology letters.

[18]  S. Dower,et al.  Binding of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist by soluble IL-1 receptors and levels of soluble IL-1 receptors in synovial fluids. , 1994, Journal of immunology.

[19]  N. Liabakk,et al.  Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo. , 1994, Blood.

[20]  G. Higgins,et al.  Interleukin 1 beta propeptide is detected intracellularly and extracellularly when human monocytes are stimulated with LPS in vitro , 1994, The Journal of experimental medicine.

[21]  F. Brennan.  Role of cytokines in experimental arthritis , 1994, Clinical and experimental immunology.

[22]  W. Arend,et al.  IgG Induction of IL‐1 Receptor Antagonist Production by Human Monocytes , 1994, Immunological reviews.

[23]  Y. Abe,et al.  Anti‐Cytokine Nature of Natural Human Immunoglobulin: One Possible Mechanism of the Clinical Effect of Intravenous Immunoglobulin Therapy , 1994, Immunological reviews.

[24]  U. Andersson,et al.  Pooled Human IgG Modulates Cytokine Production in Lymphocytes and Monocytes , 1994, Immunological reviews.

[25]  S. Frøland,et al.  Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes. , 1994, Clinical immunology and immunopathology.

[26]  K. Bendtzen,et al.  Binding of cytokines to pharmaceutically prepared human immunoglobulin. , 1993, The Journal of clinical investigation.

[27]  C. Dinarello,et al.  Measuring circulating cytokines. , 1993, Journal of applied physiology.

[28]  K. Bendtzen,et al.  Specific binding of interleukin 1 (IL-1) beta and IL-1 receptor antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to soluble IL-1 receptor type I. , 1993, Cytokine.

[29]  S. Walker,et al.  Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens [see comment]. , 1993, The Journal of clinical investigation.

[30]  P. Aukrust,et al.  Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features , 1992, Clinical and experimental immunology.

[31]  C. Dinarello,et al.  Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: II. IL-1 receptor antagonist inhibits lipopolysaccharide-induced cytokine synthesis by human monocytes. , 1992, Blood.

[32]  J. Dwyer.  Manipulating the immune system with immune globulin. , 1992, The New England journal of medicine.

[33]  M. Wewers,et al.  Sandwich ELISA formats designed to detect 17 kDa IL-1β significantly underestimate 35 kDa IL-1β , 1992 .

[34]  R. Thompson,et al.  Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. , 1991, Immunology today.

[35]  K. Bendtzen,et al.  Human anti-interleukin 1α antibodies , 1991 .

[36]  S. Misbah,et al.  Primary antibody deficiency in adults , 1991, The Lancet.

[37]  K. Bendtzen,et al.  Distribution and Characterization of Autoantibodies to Interleukin 1α in Normal Human Sera , 1990 .

[38]  H. Rollag,et al.  Impaired in vitro survival of monocytes from patients with HIV infection , 1990, Clinical and experimental immunology.

[39]  K. Lundin,et al.  RAPID IMMUNOMAGNETIC PHENOTYPING OF CELLS , 1989, Journal of immunogenetics.