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Lipopolysaccharide‐induced cytokine production and mortality in mice treated with Corynebacterium parvum
Author(s) -
Smith Sidney R.,
Calzetta Angela,
Bankowski Jennifer,
KenworthyBott Lynne,
Terminelli Carol
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.54.1.23
Subject(s) - lipopolysaccharide , tumor necrosis factor alpha , biology , cytokine , mediator , monoclonal antibody , septic shock , immunology , interleukin , interferon , microbiology and biotechnology , receptor antagonist , antibody , sepsis , receptor , antagonist , endocrinology , biochemistry
Tumor necrosis factor a (TNF‐α) has been shown to be an important mediator of the lethal effects of endotoxin in several experimental models of septic shock. However, studies with a recombinant human interleukin‐1 (IL‐1) receptor antagonist protein (IL‐lra) suggest a role for IL‐1 as a mediator of septic shock as well. In the present study, we show that mice treated in vivo with Corynebacterium parvum are primed for the production of interferon‐γ (IFN‐γ) and exhibit an enhanced capacity to produce serum IL‐Ια, TNF‐a, and IL‐6 when challenged intravenously with lipopolysaccharide (LPS). The majority of C. parvum ‐treated mice die within 24 h of an LPS challenge. Pretreatment with a rat antimouse TNF‐α monoclonal antibody (mAb) protected 90% of the animals against the lethal endotoxin challenge, while an anti‐IFN‐γ mAb gave approximately 75% protection. The anti‐IFN‐7fgamma; mAb also caused a reduction in LPS‐ induced serum TNF‐α and IL‐Ια. Anti‐IL‐la, anti‐ IL‐1β, and anti‐IL‐6 neutralizing mAb did not protect against lethality when administered to mice prior to the LPS challenge. These results indicate that TNF‐α and IFN‐γ are major mediators of endotoxin shock in C. parvum‐treated mice. The results further suggest that the IFN‐γ produced by C. parvum‐primed mice in response to an LPS challenge serves as a stimulus for enhanced production of TNF‐α and IL‐Ια. These findings are consistent with an increasing body of evidence suggesting a major role for IFN‐γ in lethal endotoxemia.