Sex differences in inflammatory cytokine production in hepatic ischemia-reperfusion

BACKGROUND: The inflammatory response to hepatic ischemia-reperfusion (I/R) is associated with an increase in cytokine production. Studies have documented that sex hormones modulate both the innate and adaptive immune responses, and that females are more robust than males. The aim of this study was to determine whether a sex difference in cytokine response to hepatic I/R exists under normal pathophysiologic condition without hormone intervention. METHODS: Adult C57BL/6 mice underwent 90 min of hepatic ischemia followed by various reperfusion periods (0, 1.5, 3, 6 hr). Plasma cytokine TNF-α, IL-6, MIP-2, and KC were measured. Liver injury was assessed by plasma alanine transaminase (ALT) levels and liver histopathology. RESULTS: A reperfusion time-dependent increase in hepatocellular injury was observed in both males and females, as indicated by increasing levels of plasma ALT and liver histopathology. The plasma cytokines were significantly increased in both female and male I/R groups compared to their respective sham counterparts. However, there was a significant difference in cytokine kinetics between the female and male I/R groups. Female mice initially had a higher level of IL-6, KC, and MIP-2 in response to I/R, which began to decline after 3 hr of reperfusion and were significantly lower than the male I/R counterparts by 6 hr of reperfusion. In contrast, the hepatocellular injury and TNF production were only moderately lower in female IR than male IR. CONCLUSION: The study underscores role of the gender in differential inflammatory cytokine expression in response to hepatic I/R, which may reflect the host response outcome

CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice

BACKGROUND: Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R). P-selectin and the intercellular adhesion molecule (ICAM)-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R. METHODS: Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null) mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study). Liver injury was assessed by plasma level of alanine aminotransferase (ALT) and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA. RESULTS: Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group. CONCLUSION: While ICAM-1 and P-selectin does not appear to be critical for neutrophil infiltration and I/R injury in the liver, they may regulate CXC-chemokine production. Blockage of these adhesion molecules may improve survival and remote organ injury that often accompanies liver I/R injury, through chemokine regulation

sj-docx-2-cpa-10.1177_07067437221147443 - Supplemental material for Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function

Supplemental material, sj-docx-2-cpa-10.1177_07067437221147443 for Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function by Daniel Kapustin, Shadi Zarei, Wei Wang, Malcolm A. Binns, Paula M. McLaughlin, Agessandro Abrahao, Sandra E. Black, Michael Borrie, David Breen, Leanna Casaubon, Dar Dowlatshahi, Elizabeth Finger, Corinne E Fischer, Andrew Frank, Morris Freedman, David Grimes, Ayman Hassan, Mandar Jog, Donna Kwan, Anthony Lang, Brian Levine, Jennifer Mandzia, Connie Marras, Mario Masellis, Joseph B. Orange, Stephen Pasternak, Alicia Peltsch, Bruce G. Pollock, Tarek K. Rajji, Angela Roberts, Demetrios Sahlas, Gustavo Saposnik, Dallas Seitz, Christen Shoesmith, Alisia Southwell, Thomas D.L. Steeves, Kelly Sunderland, Richard H Swartz, Brian Tan, David F. Tang-Wai, Maria Carmela Tartaglia, Angela Troyer, John Turnbull, Lorne Zinman, and Sanjeev Kumar in The Canadian Journal of Psychiatry</p

sj-pdf-1-cpa-10.1177_07067437221147443 - Supplemental material for Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function

Supplemental material, sj-pdf-1-cpa-10.1177_07067437221147443 for Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function by Daniel Kapustin, Shadi Zarei, Wei Wang, Malcolm A. Binns, Paula M. McLaughlin, Agessandro Abrahao, Sandra E. Black, Michael Borrie, David Breen, Leanna Casaubon, Dar Dowlatshahi, Elizabeth Finger, Corinne E Fischer, Andrew Frank, Morris Freedman, David Grimes, Ayman Hassan, Mandar Jog, Donna Kwan, Anthony Lang, Brian Levine, Jennifer Mandzia, Connie Marras, Mario Masellis, Joseph B. Orange, Stephen Pasternak, Alicia Peltsch, Bruce G. Pollock, Tarek K. Rajji, Angela Roberts, Demetrios Sahlas, Gustavo Saposnik, Dallas Seitz, Christen Shoesmith, Alisia Southwell, Thomas D.L. Steeves, Kelly Sunderland, Richard H Swartz, Brian Tan, David F. Tang-Wai, Maria Carmela Tartaglia, Angela Troyer, John Turnbull, Lorne Zinman, and Sanjeev Kumar in The Canadian Journal of Psychiatry</p