Abstract
BackgroundGold nanoparticles (AuNP) have several biochemical advantageous properties especially for a candidate of drug carrier. However, the non-conjugated AuNP has a higher rate of cellular uptake than the conjugated ones. Spherical AuNP in a proper size (20–30 nm) is non-toxic to mice and shows anti-inflammatory properties. We tested if the administration of AuNP, as an adjuvant to antibiotics, could attenuate bacterial sepsis in cecal ligation and puncture (CLP) mouse model with antibiotic (imipenem/cilastatin).ResultsIndeed, AuNP administration at the time of CLP improved the survival, blood bacterial burdens, kidney function, liver injury and inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10). AuNP also decreased M1 macrophages (CD86 + ve in F4/80 + ve cells) and increased M2 macrophages (CD206 + ve in F4/80 + ve cells) in the spleens of sepsis mice. The weak antibiotic effect of AuNP was demonstrated as the reduction of E. coli colony after 4 h incubation. In addition, AuNP altered cytokine production of bone-marrow-derived macrophages including reduced TNF-α, IL-6 and IL-1β but increased IL-10 at 6 and 24 h. Moreover, AuNP induced macrophage polarization toward anti-inflammatory responses (M2) as presented by increased Arg1 (Arginase 1) and PPARγ with decreased Nos2 (inducible nitric oxide synthase, iNos) and Nur77 at 3 h after incubation in vitro.ConclusionsThe adjuvant therapy of AuNP, with a proper antibiotic, attenuated CLP-induced bacterial sepsis in mice, at least in part, through the antibiotic effect and the induction of macrophage function toward the anti-inflammatory responses.
Highlights
Gold nanoparticles (AuNP) have several biochemical advantageous properties especially for a candidate of drug carrier
We explored if adjuvant effect of spherical gold nanoparticles (AuNP) alter macrophage functions including cytokine production and macrophage polarization
Gold nanoparticles (AuNP) attenuate cecal ligation and puncture sepsis model Due to the previous demonstration of anti-inflammatory effect of gold nanoparticles (AuNP) [7], we tested whether AuNP altered sepsis-induced mortality, renal dysfunction and liver injury in young outbred ICR mice treated with antibiotics
Summary
Gold nanoparticles (AuNP) have several biochemical advantageous properties especially for a candidate of drug carrier. Spherical AuNP in a proper size (20–30 nm) is non-toxic to mice and shows anti-inflammatory properties. We tested if the administration of AuNP, as an adjuvant to antibiotics, could attenuate bacterial sepsis in cecal ligation and puncture (CLP) mouse model with antibiotic (imipenem/cilastatin). AuNP attenuates macrophage pro-inflammatory cytokine production and spherical AuNP at the diameter of 20–30 nm is not toxic in either mice or adipose tissue macrophages [7]. Because macrophage is an important immune cell in sepsis and AuNP reduces pro-inflammatory cytokine production of macrophage, we hypothesize that the proper antibiotics in adjuvant with AuNP might attenuate sepsis severity. The effect of AuNP in sepsis was tested in a mouse model of cecal ligation and puncture (CLP) surgery with antibiotic administration. We explored if AuNP alter macrophage functions including cytokine production and macrophage polarization
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