Inhibitory effect of pooled human immunoglobulin on cytokine production in peripheral blood mononuclear cells

Kuan Hsun Wu, Wen Mein Wu, Meng Y. Lu, Bor Luen Chiang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Human intravenous immunoglobulins (IVIG) are widely used as immunomodulators because of their ability to modify the course of various immune-mediated diseases. We investigated the mechanisms responsible for the regulatory effects of IVIG on in vitro human peripheral blood mononuclear cell (PBMC) cytokine production. Pre-incubation of PBMCs with IVIG inhibited lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulated cytokine secretion. Pre-incubation of PBMCs with IVIG induced a significant inhibition of LPS-stimulated (IL-6) secretion (p = 0.045); the effect on tumor necrosis factor-α (TNF-α) secretion was not significant (p = 0.234). Pre-incubation of PBMCs with IVIG inhibited IL-6 secretion (p = 0.033) stimulated with anti-CD14 antibody cross-linking but had no significant effect on TNF-α secretion (p = 0.125). PBMC pre-incubation with anti-CD14-blocking antibody induced a significant reduction (p = 0.042) in LPS-stimulated TNF-α secretion in comparison with a non-significant reduction (p =0.256) noted with IVIG pre-treatment. In contrast, pre-incubation of PBMCs with anti-CD14 antibody did not induce a significant reduction in LPS-stimulated IL-6 secretion (p = 0.166) in comparison with a significant reduction (p = 0.001) induced with IVIG pre-treatment. Our data suggest that the immunoregulatory properties of IVIG may rely on several mechanisms, some of which may be independent of CD14. Our data also showed that cross-linking cell membrane-bound IVIG with anti-human kappa- and lambda-chain antibodies resulted in cytokine secretion levels similar to those elicited by LPS. In addition, intracellular DNA staining results did not support the involvement of apoptosis in the regulatory mechanisms of IVIG. This data may further our understanding of the immunoregulatory effects exerted by IVIG on the production of inflammatory-response mediators.

Original languageEnglish
Pages (from-to)60-68
Number of pages9
JournalPediatric Allergy and Immunology
Volume17
Issue number1
DOIs
Publication statusPublished - Feb 2006

Fingerprint

Intravenous Immunoglobulins
Immunoglobulins
Blood Cells
Cytokines
Lipopolysaccharides
Interleukin-6
Tumor Necrosis Factor-alpha
Anti-Idiotypic Antibodies
B-Cell Antigen Receptors
Ionomycin
Blocking Antibodies
Immune System Diseases
Immunologic Factors
Acetates
Cell Membrane
Apoptosis
Staining and Labeling

Keywords

  • CD14
  • Human immunoglobulin
  • Interleukin-6
  • Intravenous immunoglobulins
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pediatrics, Perinatology, and Child Health

Cite this

Inhibitory effect of pooled human immunoglobulin on cytokine production in peripheral blood mononuclear cells. / Wu, Kuan Hsun; Wu, Wen Mein; Lu, Meng Y.; Chiang, Bor Luen.

In: Pediatric Allergy and Immunology, Vol. 17, No. 1, 02.2006, p. 60-68.

Research output: Contribution to journalArticle

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KW - Tumor necrosis factor-α

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