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The present study investigated the effects of glutamine (GLN) pretreatment on CD4+ T cell polarisation and remote kidney injury in mice with gut-derived polymicrobial sepsis. Mice were randomly assigned to three groups: normal control fed with American Institute of Nutrition (AIN)-93G diet and two sepsis groups provided with either AIN-93G-based diet or identical components, except part of casein was replaced by GLN. Mice were given their respective diets for 2 weeks. Then, mice in the sepsis groups were performed with caecal ligation and puncture and were killed 72 h after the surgery. Blood, spleens and kidneys were collected for further examination. The results showed that sepsis resulted in decreased circulating and splenic total T lymphocyte and CD4+ T cell percentages, whereas IL-4-, and forkhead box p3 (Foxp3)-expressing CD4+ T cells percentages were up-regulated. Compared with the sepsis control group, pretreatment with GLN maintained blood T and CD4+ T cells and reduced percentages of IL-4- and Foxp3-expressing CD4+ T cells. Also, a more pronounced activation and increased anti-apoptotic Bcl-2 gene expression of splenic CD4+ T cells were observed. Concomitant with the decreased plasma IL-6, keratinocyte-derived chemokine (KC) levels, the gene expression of KC, macrophage inflammatory protein-2 and renal injury biomarker kidney injury molecule-1 (Kim-1) were down-regulated when GLN was administered. These findings suggest that antecedent of GLN administration elicit a more balanced blood T helper cell polarisation, sustained T cell populations, prevented splenic CD4+ T cell apoptosis and attenuated kidney injury at late phase of polymicrobial sepsis. GLN may have benefits in subjects at risk of abdominal infection.

BackgroundSepsis is a syndrome with CD4+ T‐cell dysfunction and dysregulation of T helper (Th) and regulatory T (Treg) cells. Glutamine (Gln) is a nutrient with immunomodulatory properties. This study investigated the effects of dietary Gln pretreatment on Th and Treg cell homeostasis and lung injury in mice with gut‐derived polymicrobial sepsis.MethodsMice were randomly assigned to 4 groups with 2 control (C and G) and 2 sepsis groups (SC and SG). The C and SC groups were fed a common semipurified diet, whereas the G and SG groups received an identical diet except that part of the casein was replaced by Gln. Mice were administered these diets for 2 weeks. Then mice in the control groups underwent a sham operation, whereas operations in the sepsis groups were performed with cecal ligation and puncture. Mice were killed 24 hours after the surgery. Blood, spleens, and lungs were collected for further examination.ResultsSepsis resulted in a decreased blood T‐lymphocyte percentage, whereas percentages of interferon‐γ‐expressing, interleukin (IL)‐4‐expressing, and IL‐17‐expressing CD4+ T cells were upregulated. Compared with the SC group, Gln administration before sepsis reduced blood Th1, Th2, and Th17 but increased Treg percentages. Also, percentages of CD69‐expressing CD4+ and CD8+ cells in the spleen increased. Concomitant with the decreased plasma IL‐6 and keratinocyte‐derived chemokine levels, the SG group exhibited a lower injury score of the lungs.ConclusionsPretreatment with Gln may elicit more balanced Th polarization, alleviate inflammatory response, and attenuate lung injury induced by polymicrobial sepsis.

IntroductionEfficacy and safety are critical concerns when designing drug carriers. Nanoparticles are a particular type of carrier that has gained recent attention in cancer therapeutics.MethodsIn this study, we assess the safety profile of IT-101, a nanoparticle formed by self-assembly of camptothecin (CPT) conjugated cyclodextrin-based polymers. IT-101 delivers CPT to target cancer cells in animal models of numerous human cancers and in humans. Previous data from preclinical and clinical trials indicate that IT-101 has no notable immunological side effects. However, there have been no published studies focused on evaluating the effects of IT-101 on host immune systems.ResultsIn this work, we demonstrate that IT-101 diminished initial host immune response following first injection of the nanopharmaceutical and induced NK cell activation and T cell proliferation upon further IT-101 exposure. Additionally, IT-101 could attenuate tumor growth more efficiently than CPT treatment only.ConclusionsDrugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues. Conjugated with cyclodextrin-based polymers not only reduce adverse effects but also modulate the immune responses to elevate drug efficacy. These immune responses may potentially facilitate actions of immune blockage, such as PD1/PDL1 in cancer treatment.

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