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Inflammatory Mediators in Mastitis and Lactation Insufficiency

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Abstract

Mastitis is a common inflammatory disease during lactation that causes reduced milk supply. A growing body of evidence challenges the central role of pathogenic bacteria in mastitis, with disease severity associated with markers of inflammation rather than infection. Inflammation in the mammary gland may be triggered by microbe-associated molecular patterns (MAMPs) as well as danger-associated molecular patterns (DAMPs) binding to pattern recognition receptors such as the toll-like receptors (TLRs) on the surface of mammary epithelial cells and local immune cell populations. Activation of the TLR4 signalling pathway and downstream nuclear factor kappa B (NFkB) is critical to mediating local mammary gland inflammation and systemic immune responses in mouse models of mastitis. However, activation of NFkB also induces epithelial cell apoptosis and reduced milk protein synthesis, suggesting that inflammatory mediators activated during mastitis promote partial involution. Perturbed milk flow, maternal stress and genetic predisposition are significant risk factors for mastitis, and could lead to a heightened TLR4-mediated inflammatory response, resulting in increased susceptibility and severity of mastitis disease in the context of low MAMP abundance. Therefore, heightened host inflammatory signalling may act in concert with pathogenic or commensal bacterial species to cause both the inflammation associated with mastitis and lactation insufficiency. Here, we present an alternate paradigm to the widely held notion that breast inflammation is driven principally by infectious bacterial pathogens, and suggest there may be other therapeutic strategies, apart from the currently utilised antimicrobial agents, that could be employed to prevent and treat mastitis in women.

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Abbreviations

DAMP:

Danger-associated molecular pattern

IL:

Interleukin

LPS:

Lipopolysaccharide

MAMP:

Microbe-associated molecular pattern

NOS:

Nitric oxide synthase

NFkB:

Nuclear factor kappa b

STAT5:

Signal transducer and activator of transcription 5

TLR:

Toll-like receptor

TNFA:

Tumour necrosis factor alpha

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Funding

WVI is a NBCF/THRF Fellow, MRH is an ARC Fellow [ID:110100297].

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Authors and Affiliations

  1. Discipline of Surgery, School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, Woodville, Australia

    Wendy V. Ingman & Danielle J. Glynn

  2. Robinson Research Institute, University of Adelaide, Adelaide, Australia

    Wendy V. Ingman & Danielle J. Glynn

  3. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia

    Wendy V. Ingman & Danielle J. Glynn

  4. Discipline Physiology, School of Medical Sciences, University of Adelaide, Adelaide, Australia

    Mark R. Hutchinson

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  1. Wendy V. Ingman
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  2. Danielle J. Glynn
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  3. Mark R. Hutchinson
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Correspondence to Mark R. Hutchinson.

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Ingman, W.V., Glynn, D.J. & Hutchinson, M.R. Inflammatory Mediators in Mastitis and Lactation Insufficiency. J Mammary Gland Biol Neoplasia 19, 161–167 (2014). https://doi.org/10.1007/s10911-014-9325-9

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  • DOI: https://doi.org/10.1007/s10911-014-9325-9

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