Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: Correlation with inhibition of cytokine secretion

Lior Shapira*, W. Aubrey Soskolne, Yael Houri, Vivian Barak, Amal Halabi, Ayala Stabholz

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    171 Scopus citations

    Abstract

    Septic shock results from excessive stimulation of host immune cells, particularly monocytes and macrophages, by lipopolysaccharide (LPS) released from gram-negative bacteria. Macrophage-derived cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), have been identified as central mediators in the pathogenesis of septic shock and the resultant mortality. Therefore, these cytokines were targets for experimental therapy for septic shock. Because of tetracycline's ability to intervene in cellular mechanisms involved in cytokine secretion, we tested the effect of tetracycline on LPS-induced septic shock and inflammatory lesions in mice. Tetracycline was found to protect mice against LPS-induced lethality and to abolish clinical signs of LPS-induced inflammatory lesions. This protection correlates with tetracycline's ability to reduce LPS-induced TNF-α levels in serum. Furthermore, tetracycline was found to inhibit LPS-induced TNF-α and IL-1β secretion, but not cytokine mRNA accumulation, in human monocytes in vitro. The results presented here suggest that tetracycline is a potent drug for LPS-induced pathology and that its mechanism of action involves blockage of posttranscriptional events of cytokine production.

    Original languageAmerican English
    Pages (from-to)825-828
    Number of pages4
    JournalInfection and Immunity
    Volume64
    Issue number3
    DOIs
    StatePublished - 1996

    Fingerprint

    Dive into the research topics of 'Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: Correlation with inhibition of cytokine secretion'. Together they form a unique fingerprint.

    Cite this