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Cholecystokinin protects rats against sepsis induced by Staphylococcus aureus

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Abstract

Staphylococcus aureus is a Gram-positive bacteria described as an important causative agent of sepsis. The contact between host leukocytes and bacteria activates the innate immune response. Nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-1β play a key role in increasing microbicidal activity and controlling cell influx into infectious focus. Contrarily, IL-10 acts as an anti-inflammatory cytokine and bacterial killing suppressor. Immunoregulatory properties have also been attributed to hormones, including cholecystokinin (CCK). CCK protects cardiovascular function and inhibits the inflammatory response induced by lipopolysaccharide, product derived from Gram-negative bacteria. Nevertheless, the role of CCK during Gram-positive infection remains a literature gap. Our aims were to investigate whether CCK protects rats against bacterial dissemination during sepsis induced by S. aureus. We determined whether CCK modulates local and systemic inflammatory response, as well as the cell migration into the infectious focus and the bactericidal capacity of leukocytes. Our results revealed that proglumide (nonselective CCK receptor antagonist) pretreated rats showed higher bacterial counts in blood and peritoneal lavage fluid (PLF) and reduced TNF-α and IL-10 levels in PLF. Moreover, the dissemination of S. aureus may be related to the failure of neutrophil and macrophage migration into the peritoneal cavity. Also, CCK improved the phagocytic and bactericidal ability of these inflammatory cells. Noteworthy is that the adoptive transfer of CCK-treated neutrophils and macrophages in septic rats improved immune defense, reducing bacterial number in blood and PLF. All together, our study clearly demonstrates an important protective role of CCK against sepsis induced by S. aureus.

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Acknowledgments

We would like to thank Marcelo Eduardo Batalhão for the technical assistance. The authors gratefully acknowledge the English grammar review by Renata Brancaleoni Mitchell and Ian Mitchell. This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Authors and Affiliations

  1. Department of General and Specialized Nursing, School of Nursing of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Fabiana Maria das Graças Corsi Zuelli & Evelin Capellari Cárnio

  2. Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Avenida dos Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil

    Rafael Simone Saia

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  1. Fabiana Maria das Graças Corsi Zuelli
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Zuelli, F.M.G.C., Cárnio, E.C. & Saia, R.S. Cholecystokinin protects rats against sepsis induced by Staphylococcus aureus . Med Microbiol Immunol 203, 165–176 (2014). https://doi.org/10.1007/s00430-014-0328-3

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