Abstract
IntroductionLymphocyte homeostasis is dependent on the γc cytokines. We hypothesised that sepsis in humans is associated with differential gene expression of the γc cytokines and their associated apoptosis mediators.MethodsThe study population consisted of a total of 60 patients with severe sepsis, 15 with gram negative bacteraemia, 10 healthy controls and 60 patients undergoing elective lung resection surgery. Pneumonia was diagnosed by CDC NNIC criteria. Gene expression in peripheral blood leukocytes (PBLs) of interleukin (IL)-2, 7, 15 and interferon (IFN)-γ, Bax, Bim, Bcl-2 was determined by qRT-PCR and IL-2 and IL-7 serum protein levels by ELISA. Gene expression of IL-2, 7 and IFN-γ was measured in peripheral blood leukocytes (PBL), cultured in the presence of lipopolysacharide (LPS) and CD3 binding antibody (CD3ab)ResultsIL-2 gene expression was lower in the bacteraemia group compared with controls, and lower still in the sepsis group (P < 0.0001). IL-7 gene expression was similar in controls and bacteraemia, but lower in sepsis (P < 0.0001). IL-15 gene expression was similar in the three groups. Bcl-2 gene expression was less (P < 0.0001) and Bim gene expression was greater (P = 0.0003) in severe sepsis compared to bacteraemic and healthy controls. Bax gene expression was similar in the three groups.In lung resection surgery patients, post-operative pneumonia was associated with a perioperative decrease in IL-2 mRNA (P < 0.0001) and IL-7 mRNA (P = 0.003). IL-2 protein levels were reduced in sepsis and bacteraemia compared to controls (P = 0.02) but similar in pneumonia and non-pneumonia groups. IL-7 protein levels were similar in all groups.In cultured PBLs, IFN-γ gene expression was decreased in response to LPS and increased in response to CD3ab with sepsis: IL-7 gene expression increased in response to LPS in controls and to CD3ab with sepsis; Bcl-2 gene expression decreased in response to combined CD3ab and IL-2 with sepsis.ConclusionsPatients with infection and sepsis have deficient IL-2 and IL-7 gene expression in PBLs. Aberrant cytokine gene expression may precede the onset of infection.
Highlights
Lymphocyte homeostasis is dependent on the gc cytokines
IL-2 gene expression was lower in bacteraemia patients compared with controls, and lower still in patients with sepsis (Figure 1); IL-7 gene expression was similar in control and bacteraemic patients, but lower in patients with sepsis; IL15 gene expression was similar in the three groups
IL21 messenger ribonucleic acid (mRNA) was not detected in peripheral blood leukocytes (PBLs) of any study groups
Summary
Lymphocyte homeostasis is dependent on the gc cytokines. We hypothesised that sepsis in humans is associated with differential gene expression of the gc cytokines and their associated apoptosis mediators. These cytokines act on distinct lymphocyte populations; IL-2 is a T cell growth factor, contributes to the development of regulatory T (T reg) This group has previously shown a link between effector cytokine gene expression in peripheral blood leukocytes (PBL) and human response to infection and patient response to surgery [6,7,8,9,10]. In these studies cytokine gene expression was assayed by reverse transcriptase polymerase chain reaction according to an established protocol [11] This approach provides a unique in vivo insight to PBL function in humans that may not be reflected by cytokine protein levels in peripheral blood, as these proteins may emanate from a diverse range of other cells. A secondary endpoint was to determine whether any differential gene expression of the gamma c cytokines preceded the clinical onset of infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
