Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice
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Administration of staphylococcal enterotoxin B (SEB) to BALB/c mice was found to induce a cytokine release syndrome hallmarked by weight loss and hypoglycemia. A neutralizing monoclonal antibody against gamma interferon (IFN-gamma) given before SEB counteracted weight loss and prevented hypoglycemia. This protective effect of anti-IFN-gamma antibody was associated with decreased IFN-gamma levels in serum; tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels remained unchanged. A monoclonal anti-IL-6 antibody, known for its ability to cause accumulation of biologically active IL-6 in the circulation, did not modify SEB-induced body weight loss or hypoglycemia. Levels of TNF, IFN-gamma, and IL-6 in serum were all more elevated in anti-IL-6-treated mice than in corresponding SEB-challenged control mice. In D-galactosamine-sensitized mice, SEB-induced weight loss but not hypoglycemia was more severe, resulting mostly in death within 24 h. Higher levels of biologically active TNF and IFN-gamma in serum were noted in these mice than in mice receiving SEB only. In D-galactosamine-sensitized mice, anti-IFN-gamma antibody did prevent hypoglycemia but failed to reduce the severity of the syndrome. Again, TNF levels in anti-IFN-gamma-treated mice remained unchanged. Pretreatment with anti-IL-6 antibody temporarily attenuated SEB-induced hypoglycemia in sensitized mice. Thus, at 6 h post-SEB injection, anti-IL-6-treated mice were less hypoglycemic than corresponding controls. However, at 24 h, hypoglycemia was significantly aggravated. Concomitantly, IL-6 levels were dramatically increased. Neither anti-IFN-gamma nor anti-IL-6 antibody treatment modulated mortality levels in D-galactosamine-sensitized mice. The data obtained with anti-IFN-gamma antibody clearly indicate that endogenous IFN-gamma is instrumental in bringing about hypoglycemia and body weight loss in mice exposed to SEB but also that hypoglycemia is not a crucial determinant of mortality in D-galactosamine-sensitized mice. The data obtained with anti-IL-6 antibody indicate that endogenous IL-6 is involved in regulating the levels of TNF and IFN-gamma in serum.
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Mice treated with a monoclonal anti-IL-6 antibody display increased levels of TNF.
“Mice treated with a monoclonal anti-IL-6 antibody display increased levels of TNF (34), suggesting that IL-6 may in fact counter regulate TNF levels.”
From Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle (2006) · cites this paper as [34]
Levels of TNF-α are markedly elevated in anti-IL-6-treated mice and in IL-6-deficient knockout mice, indicating that circulating IL-6 is involved in the regulation of TNF-α levels.
“and levels of TNF-α are markedly elevated in anti-IL-6-treated mice and in IL-6-deficient knockout mice [67, 68], indicating that circulating IL-6 is involved in the regulation of TNF-α levels.”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [67]
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- Authors
- Matthys, P., Mitera, T., Heremans, H., Van Damme, J., & Billiau, A.
- Affiliations
- Rega Institute for Medical Research (BE)
- Laboratory of Immunobiology, Rega Institute, University of Leuven, Belgium.
- ORCID
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 1995-04
- Volume
- 63
- Issue
- 4
- Pages
- 1158-1164
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC173128
- OpenAlex
- W1905898110
- Cited by
- 134
- References
- 26
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 3 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 8 · 2013: 5 · 2012: 6
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- staphylococcal enterotoxin B, cytokine release syndrome, interferon-gamma, interleukin-6, TNF-α, anti-IFN-gamma monoclonal antibody, anti-IL-6 monoclonal antibody, D-galactosamine sensitization, hypoglycemia, weight loss, cytokine production, mortality, endotoxin
- MeSH terms
- Animals, Body Weight, Diarrhea, Enterotoxins, Galactosamine, Hypoglycemia, Immunologic Techniques, Interferon-gamma, Mice, Inbred BALB C, Time Factors, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Superantigens, Mice
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