The role of gender in susceptibility to infection and sepsis
File(s)
Author(s)
Mohd Nasri, Noor Wahidah
Type
Thesis
Abstract
Severe sepsis results from complex and dynamic pathophysiology with mortality from sepsis remains high. Studies have shown that the immune response to infection and the incidence of sepsis differ between sexes. Standardised caecal ligation puncture (CLP) in two mice strains and different gender, namely the CD-1 and the CCR2-/- knock out mice were used to investigate possible gender differences in several aspects, including the survivability, the cardiovascular changes and immunological characteristics. Survival study between CLP-induced sepsis resulted in a significantly lower survival rate in males compared to females (p<0.001). In the CCR2-/- mice, higher mortality rate in female CLP CCR2-/- compared to female CD-1 mice (p<0.001). Hypothermia, one of the hallmark of sepsis-induced systemic inflammation was severely decreased in male CLP CD-1 compared to female CD-1 mice at 12 h (p<0.001) and at 16 h and 24 h (p<0.0001 respectively). In the CCR2-/- mice, male CLP CCR2-/- showed hypothermia at 8 h and 12 h (p<0.0001 respectively), while in female CLP CCR2-/- at 12 h and 16 h (p<0.0001 respectively) in comparisons with CD-1 groups. Male CLP CD-1 mice showed significant changes of hypotension and haemodynamic dysfunction compared to female CLP CD-1. CCR2-/- mice showed significant cardiovascular changes compared to CD-1 groups. The neutrophils and monocytes were found to be increased mostly in male CLP CD-1 compared to female CLP CD-1. Higher amount of these cells were observed in male and female CLP CD-1 compared to CCR2-/- mice strains. Inflammatory markers expression were found to be higher in male CLP CCR2-/- compared to male CLP CD-1. Interestingly, bacterial accumulation was found to be greater in male CLP of both strains. We concluded that failure to eradicate the invading bacteria might be responsible for male mice susceptibility and succumb to death.
Version
Open Access
Date Issued
2023-02-13
Date Awarded
2023-06-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Johnson, Mark
Sponsor
Kementerian Pengajian Tinggi Malaysia
Universiti Kebangsaan Malaysia
Publisher Department
Department of Metabolism, Digestion and Reproduction
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)