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Updated: Aug 12, 2026

Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
The effects of IgG and immune complexes on the endotoxin-induced cytokine response
S M Yentis1, R P Gooding, P G Riches
1Department of Anaesthesia, Chelsea & Westminster Hospital, London, UK.
Insights
This study shows that endotoxin (LPS) and IgG immune complexes induce cytokines like IL-6, but the presence of complement activation and serum alters these responses, affecting IL-6 and TNF-alpha production.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Cytokine induction is crucial in immune responses.
- Endotoxin (LPS) and IgG are key immune activators.
- The role of complement and serum in modulating these responses requires further investigation.
Purpose of the Study:
- To investigate cytokine induction (IL-1 beta, IL-6, TNF-alpha) in human whole blood stimulated by LPS and IgG.
- To determine the influence of different media (plasma, serum, CSL) and complement activation on these inductions.
- To analyze the effect of LPS/IgG immune complexes on cytokine profiles.
Main Methods:
- Human peripheral whole blood cells were suspended in autologous plasma or serum diluted in basal medium or Compound Sodium Lactate Solution (CSL).
- Cells were stimulated with LPS, IgG (Sandoglobulin), or preformed LPS/IgG immune complexes.
- Cytokine levels (IL-1 beta, IL-6, TNF-alpha) and complement activation were measured.
Main Results:
- LPS alone induced all three cytokines.
- Sandoglobulin alone induced IL-6 in CSL-serum and TNF-alpha in plasma, with minimal IL-1 beta changes.
- LPS/IgG immune complexes, in the presence of complement activation and/or serum, increased IL-1 beta and IL-6 while decreasing TNF-alpha, dissociating their production patterns.
Conclusions:
- Complement activation and serum significantly modulate cytokine induction by LPS and IgG.
- Sandoglobulin can induce IL-6 and suppress TNF-alpha under specific conditions (complement/serum presence).
- Immune complex formation with LPS leads to a dissociation of IL-1 beta/IL-6 from TNF-alpha production when complement is activated.
Abstract:
Cytokine induction following stimulation by endotoxin (LPS) was investigated in human peripheral whole blood. Blood cells were suspended in autologous plasma diluted in basal medium (BM-plasma) or Compound Sodium Lactate Solution (CSL-plasma), or in autologous serum diluted in CSL. Induction of interleukin 1 beta, interleukin 6 and tumour necrosis factor alpha (IL-1 beta, IL-6 and TNF-alpha, respectively) was investigated following incubation of blood cells with LPS, IgG (Sandoglobulin) alone, or preformed LPS/IgG immune complexes. All three cytokines were induced by LPS alone. With 30 mg/ml Sandoglobulin alone, IL-1 beta production changed little from control, whilst IL-6 production increased markedly in CSL-serum only. TNF-alpha production increased slightly in BM-plasma and CSL-plasma, but not in CSL-serum. Lower concentrations of Sandoglobulin did not affect cytokine production. Upon stimulation with LPS/Sandoglobulin immune complexes, a trend in cytokine production was seen compared with the response to LPS alone: IL-1 beta and IL-6 production increased, whilst TNF-alpha production decreased. This only occurred in CSL-plasma and CSL-serum. Complement activation was present only in CSL-plasma and CSL-serum. Thus in the presence of complement activation and/or serum, Sandoglobulin can induce IL-6 production whilst suppressing the small TNF-alpha response it otherwise stimulates. In addition, when LPS is presented in the form of IgG immune complexes, dissociation of IL-1 beta and IL-6 production from TNF-alpha production is seen but only in the presence of complement activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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