Cholecystokinin protects rats against sepsis induced by Staphylococcus aureus.
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.
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
FM
Zuelli
Evelin Capellari
EC
Cárnio
Rafael Simone
RS
Saia
D000818:Animals; D058491:Bacterial Load; D001769:Blood / Q000382:microbiology; D001826:Body Fluids / Q000276:immunology; D002766:Cholecystokinin / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000032:analysis; D008297:Male; D010529:Peritoneal Cavity / Q000382:microbiology; D017208:Rats, Wistar; D018805:Sepsis / Q000382:microbiology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002766:Cholecystokinin