AUTHOR=de Souza Paula R. Knox , Ferreira Sabrina S. , Nunes Fernanda P. B. , Casagrande Felipe B. , Tessaro Fernando H. G. , Silva Mariana C. F. , Cruz José Walber Miranda Costa , Mamizuka Elsa M. , Martins Joilson O. 

TITLE=Cytokine and Adhesion Molecule Expression Induced by Different Strains of Staphylococcus aureus in Type 1 Diabetic Rats: Role of Insulin

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.03165

DOI=10.3389/fimmu.2018.03165

ISSN=1664-3224

ABSTRACT=<p><bold>Introduction:</bold><italic>Staphylococcus aureus</italic> may provoke peritonitis and death, especially in immunocompromized individuals such as diabetic patients. We evaluated the role of insulin in <italic>S. aureus</italic>-induced peritoneal infection in diabetic and non-diabetic rats.</p><p><bold>Materials/Methods:</bold> Alloxan-diabetic male Wistar rats and their respective controls received intraperitoneal injections of different strains of <italic>S. aureus</italic> or sterile phosphate-buffered saline. After 3 days of infection, the first set of diabetic and non-diabetic rats received 4 and 1 IU, respectively, of neutral protamine Hagedorn insulin and were analyzed 8 h later. The second set of diabetic and non-diabetic rats received 4 and 1 IU, respectively, of insulin 2 h before intraperitoneal infection and a half dose of insulin at 5 p.m. for the next 2 days and were analyzed 16 h later. The following measurements were performed: (a) number of cells in the peritoneal lavage fluid (PeLF), white blood cell count, and blood glucose; (b) serum insulin and corticosterone; (c) cytokine levels in the PeLF; (d) expression of adhesion molecules in the vascular endothelium; and (e) microbicidal activity.</p><p><bold>Results:</bold> Diabetic rats showed an increased number of polymorphonuclear leukocytes (PMNs) and increased concentrations of CINC-1, IL-4, and IFN-γ in the PeLF after infection with the ATCC 25923 or N315 αHL<sup>+</sup> strain. The mesenteric expression of PECAM-1 was increased after infection with the N315 HLA<sup>+</sup> strain. ICAM-1 expression was increased with ATCC infection. Treatment of diabetic rats with a single dose of insulin restored CINC-1 levels in the PeLF for both strains; however, PMN migration, IL-4, and IFN-γ were restored in rats infected with the ATCC strain, whereas the PeLF concentrations of CINC-2, IL-1β, and IL-4 were increased in N315-infected animals. Insulin restored PMN migration and CINC-2 levels in the PeLF in ATCC-infected rats. After multiple treatments with insulin, the levels of IL-1β, IL-6, and IFN-γ were increased in the PeLF of diabetic rats after infection with either strain, and CINC-2 levels were restored in N315-infected animals.</p><p><bold>Conclusion:</bold> These results suggest that insulin distinctively modulates cytokine production or release, PMN leukocyte migration, and adhesion molecule expression during the course of peritonitis induced by different strains of <italic>S. aureus</italic>.</p>