title: The effect of Intravenous Immunoglobulin (IVIG) on \textit{ex vivo} activation of human leukocytes.
abstract: BACKGROUND
  Intravenous immunoglobulin (IVIG) has been widely used to treat various conditions, including inflammatory and autoimmune diseases. IVIG has been shown to have a direct influence on neutrophils, eosinophils and lymphocytes. However, many aspects IVIG's effect on neutrophils activation still remain unknown.
  
  
  OBJECTIVE
  To evaluate the effect of IVIG on PMA-induced activation of neutrophils, with and without priming with TNF-α, in a series of in vitro experiments performed on whole blood.
  
  
  RESULTS
  Our data coincided with well-known literature indicating that the effect of phorbol 12-myristate 13-acetate (PMA) on human leukocytes includes activation of neutrophils, monocytes and eosinophils, increase of chemiluminescence (CL) and induction of netosis, resulting in assembly of traps. In presence of IVIG (10 mg/mL), CL was reduced by 25% in response to PMA compared to PMA-induced leukocyte activation without IVIG. Decreasing IVIG concentration to 1 mg/mL and below did not inhibit PMA-induced activation of CL.PMA-induced activation after TNF-α priming resulted in approximately 50% increase of amplitude of CL response to PMA. Moreover, maximum CL was reached by minute 5, which was more rapid than in the absence of TNF-α-priming (in this case maximum CL was reached by minute 15).The IVIG concentrations did not affect morphological changes of leukocytes after sequential addition of TNF-α and PMA. IVIG had no effect on leukocyte content and on PMA-induced CL of primed leukocytes.Addition of IVIG under TNF-α priming significantly increased the number of traps in the smears in response to PMA activation. Of note, such an increase in the number of traps was depended on the IVIG concentration in plasma.
  
  
  CONCLUSIONS
  In conclusion, we suggest that IVIG is able to reduce the degradation of traps under priming with TNF-α. Moreover, IVIG might switch the activation of primed leukocytes to netosis.
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
authors.forename: Liliya Yu
authors.initials: LY
authors.lastname: Basyreva
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
authors.forename: Ilya B
authors.initials: IB
authors.lastname: Brodsky
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Gusev
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Zhapparova
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Mikhalchik
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Gusev
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Department of Gastroenterology, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Dana Ben-Ami
authors.initials: DB
authors.lastname: Shor
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Dahan
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Blank
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D004306:Dose-Response Relationship, Immunologic; D065206:Extracellular Traps / Q000187:drug effects / Q000276:immunology; D064368:Healthy Volunteers; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008163:Luminescent Measurements; D008213:Lymphocyte Activation / Q000187:drug effects; D061251:Primary Cell Culture; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016756:Immunoglobulins, Intravenous; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate
keywords: Intravenous Immunoglobulin (IVIG); TNF-α; autoimmunity; leukocytes; neutrophils; priming