Impaired Nonspecific Cellular Immunity in Experimental Cholestasis

Roughneen, Patrick T.; Drath, David B.; Kulkarni, Anil D.; Rowlands, B. J.

doi:10.1097/00000658-198711000-00004

Cited by 43 publications

(18 citation statements)

References 18 publications

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“…Defective PMN phagocytic function with obstructive jaundice and impaired PMN superoxide release function by bilirubin and bile acids challenge has been demonstrated in animal studies (16,22). However, no PMN dysfunction, including superoxide release, phagocytic function, absolute neutrophil cell number, and proportion of basal expression of leukocyte adhesion molecule (CD11b/CD18 complex) was identified in our study.…”

Section: Discussioncontrasting

confidence: 48%

Impaired T-Lymphocyte Proliferation Function in Biliary Atresia Patients With Chronic Cholestatic Jaundice After a Kasai Operation

Chiang

Chen

et al. 2006

Pediatr Res

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ABSTRACT:To investigate the association between chronic cholestatic jaundice, systemic immunity, and various infectious complications in patients with biliary atresia (BA), we performed a survey of the systemic immune function in 30 children with BA. Patients were divided into a jaundice group (total serum bilirubin Ն2 mg/dL for Ͼ6 mo) and control group (total serum bilirubin Ͻ2 mg/dL for Ͼ6 mo) with comparable age. Patients were tested for serum immunoglobulin and complement levels, mitogen response, interleukin (IL)-4, IL-5, and interferon-gamma production after phytohemagglutinin (PHA) stimulation, blood cell and lymphocyte subpopulation counts, phagocytic function, and leukocyte adhesion complex. They were then followed prospectively for 6 mo, and severe infectious complications requiring hospitalization were recorded. Compared with jaundice-free patients, T-lymphocyte proliferation function, determined by PHA mitogen test was significantly lower (p ϭ 0.02) in BA patients with chronic cholestatic jaundice after a Kasai operation. During the study period, patients with chronic cholestatic jaundice had a higher risk of severe infectious complications than their jaundice-free counterparts (risk ratio ϭ 5.87; p ϭ 0.001). In conclusion, BA patients with chronic cholestatic jaundice are associated with impairment of T-lymphocyte proliferation and increased incidence of severe infectious complications.

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Section: Discussioncontrasting

confidence: 48%

Impaired T-Lymphocyte Proliferation Function in Biliary Atresia Patients With Chronic Cholestatic Jaundice After a Kasai Operation

Chiang

Chen

et al. 2006

Pediatr Res

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“…munosuppression characterizing cholestatic conditions [5][6][7][8] and In this study, CDCA and UDCA were selected as two protoin Table 4, in comparison with that of [ 3 H]-thymidine as a type bile acid molecules with divergent physico-chemical control. The data show that CDCA uptake, both at 40 mmol/ characteristics, 35 to test their ability to influence the produc-L and 200 mmol/L concentration of the bile acid, was inversely tion of IL-6 and TNFa from monocytes and Kupffer cells.…”

Section: Discussionmentioning

confidence: 99%

Bile acids with differing hydrophilic-hydrophobic properties do not influence cytokine production by human monocytes and murine Kupffer cells

et al. 1997

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conclusion, bile acids with widely different hydrophobiBile acids have been proposed to exert immunological cities are incapable of influencing the release of IL-6 and effects of potential pathogenic or therapeutic relevance, TNFa by monocytes and Kupffer cells, provided they are yet the experimental evidence remains preliminary. We studied at noncytotoxic concentrations and in the presreexamined the effects of a variety of bile salts with difence of physiological amounts of proteins. (HEPATOLOGY fering hydrophilic-hydrophobic properties on the pro-1997;25:927-933.) duction of interleukin-6 (IL-6) and tumor necrosis factor a (TNFa) from monocytes and Kupffer cells. Monocytes from healthy human donors and Kupffer cells from 5-Infectious complications 1,2 and endotoxemia 3,4 occur freweek-old mice were incubated for up to 18 hours with quently in patients with severe cholestasis. The underlying or without varying concentrations of bile salts and lipo-mechanisms are not fully understood, yet cholestasis may be polysaccharide (LPS). Monocyte viability was ¢95% with the consequence of the impairment of cell-mediated immuup to 250 mmol/L sodium ursodeoxycholate and°90% nity 5-7 and macrophage function. 8 Endotoxins are lipopolysacwith 200 mmol/L chenodeoxycholate, decreasing sharply charides (LPS) present in the wall of gram-negative bacteria. at higher concentrations. Kupffer cells were more vul-Endotoxemia may derive from both systemic infections with nerable, particularly to chenodeoxycholate (viabilities gram-negative bacteria or from absorption of LPS from the of 25% and 0% at concentrations of 100 mmol/L and 200 gut. Normally, LPS is cleared by liver macrophages (Kupffer mmol/L, respectively). In monocytes incubated in the cells), but when their phagocytic function is impaired, as in presence of 20% fetal calf serum, neither ursodeoxycho-cholestasis, or an excessive amount of LPS is being delivered late and chenodeoxycholate, nor a variety of other un-from the intestine, endotoxins may spill over into the periphconjugated and conjugated bile acids, tested up to their eral circulation. LPS stimulates both circulating and tissue maximal noncytotoxic concentrations, influenced the macrophages to release several cytokines, 9,10 known to be po-IL-6 and TNFa production, at any level of LPS stimula-tent inflammatory mediators, 11 as well as activators of a comtion. Similar to monocytes, incubation of murine Kupffer plex immuno-metabolic cascade, 12-14 mimicking the effects of cells with ursodeoxycholate and chenodeoxycholate did acute infections. 15 This establishes a vicious cycle, aggravatnot influence cytokine release. In contrast, the addition ing the original cholestasis and often leading to multiple orof 10 nmol/L dexamethasone to monocytes significantly gan failure. On the other hand, during bacterial sepsis, the decreased TNF-a and IL-6 release (69 { 11% and 48 { liver is the main organ responsive to LPS, 16 presumably be-15%, respectively). When monocytes were incubated cause Kupffer cells are the major source...

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“…Absence of intestinal bile appears to be central to the function [23], cell-mediated immunity [24], and Kuppfer cell function [25], may relate to intestinal gramcompromised gut barrier function in experimental obstructive jaundice. The association of bile duct obstruc-negative bacteria and endotoxin.…”

Section: Discussionmentioning

confidence: 99%