Exploration on survived mice after sepsis and proteomic analy-sis on LPS-activated macrophages supports the regulation of sepsis hyper-inflammation by intravenous immunoglobulin

ABSTRACT: Because the immune regulation in survivor after sepsis (an immune dysregulation from severe infection) might be applied for treatment, survivors and moribund mice after cecal liga-tion and puncture (CLP) and in vitro experiments on macrophages were explored. Most of the parameters in survivors (5-days post-CLP) were normalized, except for the slightly increase in alanine transaminase, IL-10, lipopolysaccharide (LPS) and gut leakage (FITC-dextran assay), with the enhanced adaptive immunity; serum immunoglobulin (using serum protein electrophoresis) and activated immune cells in spleens (flow cytometry analysis). Then, a clue to surviving sepsis may be effective innate immunity regulation by adaptive immune responses. Indeed, soluble heat aggregated immunoglobulin (sHA-Ig, a representative of immune complex) in LPS-activated macrophages reduced supernatant cytokines and down-regulated proteins in sev-eral processes (using proteomic analysis). As a proof of concept, intravenous immunoglobulin (IVIG) attenuated sepsis severity in CLP mice as evaluated by serum creatinine, ALT, serum cy-tokines, spleen apoptosis (24 h post-CLP) and 48 h survival analysis. In conclusion, immuno-globulin may play a role in sepsis immune hyper-responsiveness. Despite the debate over IVIG's use in sepsis, adequate selection criteria for sepsis patients who may benefit the most from IVIG could lead to an increase use of this clinically viable treatment.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Macrophage

SUBMITTER: Jiradej Makjaroen  

LAB HEAD: Asada Leelahavanichkul

PROVIDER: PXD027471 | Pride | 2022-02-22

REPOSITORIES: Pride