Effects of glutamine supplementation on gut barrier,glutathione content and acute phase response in malnourished rats during inflammatory shock

AIM: To evaluate the effect of glutamine on intestinal mucosa integrity,glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels,liver and jejunal glutathione concentrations were measured before and one,three and seven days after turpentine injection in 4 groups of control,protein-restricted,protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height,and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil,glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue,P < 0.05) in the jejunum,whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate(0.02 mg/kg) or free dexamethasone(0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide(LPS)(2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-a(TNF-a) and interleukin 6(IL-6) 2 h post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin(a-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects.RESULTS: The conjugate halved the a-2-M liver m RNA(3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein(201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver m RNA or serum levels of a-2-M. Also, the conjugate reduced TNF-a(7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6(15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight(421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other group.CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.

Acute Phase Response of Rabbit to HgCl_2 and CdCl_2

A variety of changes occur in the rabbit under metal stress which include the appearance of the acute phase protein, C-reactive protein in the serum and significant reduction in the serum litres of albumin and acetylcholinesterase. The phospholipid profile is positively correlated with the higher degree of tissue necrosis encountered in mercury treated rabbit. Cadmium and mercury treatments evoke a similar response pattern in rabbit differing only in the degree of change.

Inflammation: Complexity and significance of cellular and molecular responses

Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.

Microheterogeneity of acute phase proteins in patients with uIterative colitis

AIM： TO estimate the serum α1-antichymotrypsin （ACT）, α1-acid glycoprotein （AGP） and transferrin （Tf） concentrations and to evaluate the microheterogeneity of these acute phase proteins in patients with ulcerative colitis. METHODS： Twenty-seven patients with ulcerative colitis （UC） and 17 healthy control subjects were studied. The patients were categorised as severe （n = 9）, moderate （n = 10） and mild groups （n = 8） using Truelove and Witts＇ classification of ulcerative colitis. Microheterogeneity of ACT, AGP and Tf was analysed by crossed immunoaffinity electrophoresis （CIAE） with concanavalin A. In all serum samples standard electrophoresis of serum proteins was performed, iron （Fe） concentration, total iron binding capacity （TIBC） and C-reactive protein （CRP） were also measured. RESULTS： Our patients suffering from ulcerative colitis had significantly higher serum ACT and AGP concentrations and lower serum transferrin concentration in comparison to healthy subjects. Changes in concentrations of acute phase proteins were dependent on the activity of the inflammatory process. The glycosylation patterns of transferrin were related to the inflammation status. We also observed the correlation between ACT and AGP concentrations, patterns of transferrin glycosylation and changes in standard protein electrophoresis or blood cell count. CONCLUSION： The glycosylation patterns of transferrin obtained from patients suffering from ulcerative colitis are highly branched and sialylated compared with those obtained from healthy subjects. In contrast, the glycosylation patterns of transferrin do not differ according to the activity index of ulcerative colitis. The microheterogeneity patterns of AGP and ACT are similar in ulcerative colitis patients and healthy subjects.

Breed and adaptive response modulate bovine peripheral blood cells＇ transcriptome

Background： Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins（APPs） are reactants synthesized against environmental stimuli like stress, infection, inflammation.Methods： To delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein（IH） and Italian Simmental（IS） breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals（five APP＋ and APP-variants） from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed（DE） genes were analyzed using dynamic impact approach（DIA）and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP＋ and APP-gene expression patterns with variations in milk parameters.Results： The overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP＋ vs. all APP-variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism.Conclusions： Both DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP＋ and APP-variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP＋ and APP-gene expression patterns.

Response to lipopolysaccharide in Octodon degus pups produces age-related sickness behavior but does not have effects in juveniles

During vertebrate development,the immune function is inefficient and is mainly controlled by innate defense.While there have been detailed studies of various aspects of innate immune function,the effects of this func­tion in the growth of vertebrates is still not well known.Similarly,there is little information regarding how ear­ly endotoxin exposure would affect juvenile phenotypes,specifically in a non-model mammal like a precocial rodent.We evaluated the response to an antigen and its cost in offspring of the rodent Octodon degus.We in­oculated pups at 4 different ages(8,15,22 and 30 days after birth)with an antigen to determine the ontogeny and costs of the response to an endotoxin.We assessed changes in body mass,body temperature,sickness be­havior and the levels of a key mediator of the inflammatory response,the cytokine interleukin-1β.We also de­termined the effects of early endotoxin exposure on the resting metabolic rate of juvenile animals(i.e.90 days after birth).The cytokine levels,body mass and body temperature were unaffected by time of inoculation and treatment.However,pups subjected to inoculation at 22 days after birth with the antigen showed reduced loco­motion.Juvenile resting metabolic rate was not affected by early endotoxin exposure.These results suggest that the magnitude of O.degus responses would not change with age.We discuss whether the lack of effect of the response on body mass or body condition is caused by environmental variables or by the precocial characteris­tics of O.degus.

Hepatic cecum:a key integrator of immunity in amphioxus

The vertebrate liver is regarded as an organ essential to the regulation of immunity and inflammation as well as being central to the metabolism of nutrients.Here,we discuss the functions that the hepatic cecum of amphioxus plays in the regulation of immunity and inflammation,and the molecular basis of this.It is apparent that the hepatic cecum performs important roles in the immunity of amphioxus including immune surveillance,clearance of pathogens and acute phase response.Therefore,the hepatic cecum,like the vertebrate liver,is an organ functioning as a key integrator of immunity in amphioxus.