Search PubMed⌕ Search

Biomedical subjects

B K King

Publications and source records attributed to B K King.

9 recordsLinked to original sources
PubMed2001

Impairment of mucosal immunity by total parenteral nutrition: requirement for IgA in murine nasotracheal anti-influenza immunity.

Secretory IgA (SIgA) is the primary mucosal Ig and has been shown to mediate nasotracheal (NT) mucosal immunity in normal immune BALB/c mice. This finding has been challenged by a report of NT immunity without IgA in knockout mice, suggesting that IgA may not be necessary for the protection of mucosal surfaces. Although other protective mechanisms may become active in the congenital absence of SIgA, these mechanisms are not the primary means of protection in normal mice. In this paper we show that feeding chemically defined total parenteral nutrition (TPN) to genetically normal, immune ICR mice by the i.v. route results in loss of nasal anti-influenza immunity and a significant drop in influenza-specific SIgA in the upper respiratory tract compared with chow-fed mice (p < 0.005), while the serum influenza-specific IgG titer is unaffected. Loss of upper respiratory tract mucosal immunity is not related to serum Ab, because 10 of 13 TPN-fed mice shed virus into their nasal secretions despite adequate serum anti-influenza IgG titers. The number of IgG Ab-secreting cells in the nasal passages and spleens of TPN-fed mice was unaffected, while both the number and the percentage of splenic IgA-secreting cells were decreased relative to those in chow-fed animals. The loss of immunity is due to the route of nutrition, not the composition of the diet, because TPN solution fed orally via gastrostomy instead of i.v. maintains NT anti-influenza mucosal immunity. We hypothesize that delivery of nutrition via the gut triggers the release of gastrointestinal neuropeptides necessary for maintenance of the mucosal immune system.

Administration, Intranasal↗
PubMed2001

Impairment of mucosal immunity by parenteral nutrition: depressed nasotracheal influenza-specific secretory IgA levels and transport in parenterally fed mice.

OBJECTIVE: To examine the effects on mucosal selective transport of polymeric IgA (pIgA) and the ability of exogenous pIgA to provide protection despite altered mucosal transport. SUMMARY BACKGROUND DATA: Parenteral nutrition significantly impairs established antipseudomonal immunity and IgA-mediated antiviral immunity in association with gut-associated lymphoid tissue mass atrophy. Lack of enteral feeding also induces mucosal effects. METHODS: After immunization, nasotracheal levels of influenza-specific IgA were measured in cannulated mice randomized to chow feeding or parenteral nutrition. Nonimmune animals were randomized to chow or total parenteral nutrition, and after 5 days of diet were given a mixture of two antiinfluenza monoclonal antibodies, pIgA and IgG. Four hours after injection, nasal washes were collected and influenza-specific antibody levels were determined by enzyme-linked immunosorbent assay to calculate the selective transport index of IgA relative to IgG. In the final experiment, immunized animals were randomized to chow or parenteral feeding, and after 5 days, parenterally fed animals received either normal mouse serum or antiviral pIgA before viral challenge. Viral shedding was measured at 42 hours after challenge. RESULTS: Parenteral nutrition significantly reduced virus-specific IgA in nasotracheal washes. Parenteral nutrition depressed the selective transport index, demonstrating impaired mucosal transport of pIgA. Parenterally fed animals given specific antiviral pIgA but not normal mouse serum eliminated virus from the airway and regained mucosal protection, demonstrating adequate residual transport for immunity if adequate pIgA is present. CONCLUSION: Although both decreased IgA production due to gut-associated lymphoid tissue atrophy and impaired mucosal transport occur when enteral feeding is not provided, residual transport can provide antiviral protection if exogenous antiviral pIgA is available. Production, rather than transport, may be the most important factor in maintaining established respiratory tract IgA-mediated immunity.

Analysis of Variance↗
PubMed2000

Bombesin recovers gut-associated lymphoid tissue and preserves immunity to bacterial pneumonia in mice receiving total parenteral nutrition.

OBJECTIVE: To study the ability of bombesin (BBS) to recover gut-associated lymphoid tissue (GALT) and preserve immunity in a lethal model of Pseudomonas aeruginosa (Ps) pneumonia in mice receiving total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: TPN causes depression of mucosal immunity compared with enterally fed animals, which may explain the increased incidence of pneumonia in parenterally fed trauma patients. BBS prevents this TPN-induced GALT atrophy, depressed gastrointestinal and respiratory tract IgA levels, and impaired antiviral IgA-mediated mucosal immunity. The authors examined whether some supplement could be added to TPN to avoid this GALT atrophy and lower the incidence of infectious complications in the parenterally fed animal. METHODS: Male mice were randomized to chow or intravenous (IV) TPN. After 5 days of IV TPN, mice received 0, 1, 2, or 3 days of BBS IV three times a day and then were killed to harvest Peyer's patch, intraepithelium, and lamina propria for cell yields. Gastrointestinal and respiratory tract IgA levels were analyzed by enzyme-linked immunosorbent assay. Next, mice underwent intranasal inoculation with liposomes alone (nonimmune) or liposome-containing Ps polysaccharide. Ps immune mice were catheterized and randomized to chow, IV TPN, or IV TPN + BBS. The liposome group received chow but no IV catheter. These mice were given an LD90 dose of intratracheal Ps, and death rates were recorded. RESULTS: GALT and gastrointestinal and respiratory tract IgA levels improved to those in chow-fed mice after 3 days of BBS. Immunization reduced the death rate from 92% in chow-fed liposome-only animals to 20% in immunized animals. TPN-fed animals lost their mucosal immunity, with a death rate of 86% compared with 21% in the TPN + BBS group. CONCLUSION: The results demonstrate that BBS reverses TPN-induced changes in GALT and preserves mucosal immunity. Ps immunization reduces the death rate in a gram-negative pneumonia model and maintains gastrointestinal and respiratory immunity in Ps immune mice receiving IV TPN.

Animals↗
PubMed1999

Route and type of nutrition influence mucosal immunity to bacterial pneumonia.

OBJECTIVE: To develop a model of established respiratory immunity against Pseudomonas aeruginosa pneumonia and to investigate the effects of route and type of nutrition on this immunity. SUMMARY BACKGROUND DATA: Diet influences the ability of gut-associated lymphoid tissue (GALT) to maintain mucosal immunity. Complex enteral diets and chow maintain normal GALT populations against established IgA-mediated antiviral respiratory immunity. Both intravenous and intragastric total parenteral nutrition (TPN) produce GALT atrophy, but only intragastric TPN preserves established antiviral immunity. The authors hypothesized that both GALT-depleting diets (intragastric and intravenous TPN) would impair immunity against bacterial pneumonia. METHODS: P. aeruginosa was administered intratracheally to determine the mortality rate at increasing doses, and liposomes containing P. aeruginosa antigens were used to generate effective respiratory immunization. In the final experiment, mice received liposomes containing P. aeruginosa antigens to establish immunity and then were randomized to chow, complex enteral diets, intragastric TPN, or intravenous TPN. After 5 days of diet, mice received live intratracheal P. aeruginosa, and the death rate was recorded at 24 and 48 hours. RESULTS: The LD50 and LD100 were 9 x 10(7) and 12 x 10(7), respectively. Immunization reduced the mortality rate from 66% to 12%. This immunization was maintained in mice fed chow or a complex enteral diet and was lost in animals receiving intravenous TPN. Intragastric TPN partially preserved this respiratory immunity. CONCLUSIONS: Protection against bacterial pneumonia can be induced by prior antigenic immunization. This protection is lost with intravenous TPN, partially preserved with a chemically defined enteral diet, and completely preserved with chow or complex enteral diets. Both route and type of nutrition influence antibacterial respiratory tract immunity.

Animals↗
PubMed1997

A temporal study of TPN-induced changes in gut-associated lymphoid tissue and mucosal immunity.

BACKGROUND: Total parenteral nutrition (TPN) is associated with decreases in small-intestinal gut-associated lymphoid tissue (GALT) T cells, B cells, and IgA levels and impairs IgA-mediated defenses in the respiratory tract. The impaired respiratory tract defenses are speculated to be due to reduced respiratory tract IgA levels. OBJECTIVES: To determine the time course of GALT cell reductions and document any changes in respiratory tract IgA levels in mice receiving TPN. DESIGN: Prospective randomized trial. SETTING: Animal research laboratory. MATERIALS: Thirty-five male ICR mice weighing 25 to 35 g. INTERVENTIONS: Mice underwent cannulation with intravenous catheters and received chow for 2 days followed by TPN for 0 (n=6), 1 (n=6), 2 (n=6), 3 (n=6), 4 (n=6), or 5 (n=5) days. Mice were killed after receiving TPN their respective number of days. The small intestine was harvested, and washings were obtained from the small intestine and the respiratory tract. Lymphocytes and IgA levels were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. MAIN OUTCOME MEASURES: Lymphocyte yields from Peyer patches, intraepithelial spaces, and the lamina propria; IgA levels from the small intestine and the respiratory tract. RESULTS: T- and B-cell yields in the Peyer patches and lamina propria were significantly reduced by day 2 (P<.05) and thereafter compared with day 0. The lamina propria CD4+/CD8+ ratio declined significantly by day 4 (P<.05) compared with day 0. Small-intestinal and respiratory tract IgA levels were significantly diminished by day 3 (P<.05) and thereafter compared with day 0. CONCLUSION: Total parenteral nutrition produces rapid changes in GALT cell profiles and reduces respiratory tract IgA levels consistent with the impairment of respiratory IgA-mediated defenses.

Animals↗
PubMedDate not supplied

Wegener's granulomatosis causing laryngeal and tracheobronchial obstruction in an adolescent girl.

A 12-year-old girl presenting with a painful neck mass and ulcerated gingival lesions was found to have Wegener's granulomatosis involving the gingivae, paranasal sinuses, ears, mastoids, larynx, trachea, bronchial tree, lungs, kidneys and joints. The initial illness and two subsequent exacerbations were treated with intravenous and oral cyclophosphamide and prednisone. Secondary infections have been managed with establishment of good drainage and use of appropriate antibiotics. The patient is well with a normal sedimentation rate 4 1/2 years after the onset of her disease.

Airway Obstruction↗
PubMedDate not supplied

Glycyl-L-glutamine-enriched total parenteral nutrition maintains small intestine gut-associated lymphoid tissue and upper respiratory tract immunity.

BACKGROUND: i.v. administration of a total parenteral nutrition (TPN) solution results in small intestinal gut-associated lymphoid tissue (GALT) atrophy, lowers small intestinal immunoglobulin A (IgA) levels, and impairs upper respiratory tract secretory IgA-mediated mucosal immunity; isonitrogenous supplementation of TPN with 2% glutamine attenuates these changes. This experiment examines whether a 2% glycyl-L-glutamine-enriched TPN solution reverses i.v. TPN-induced changes as effectively as L-glutamine. METHODS: Male Institute of Cancer Research (ICR) mice underwent intranasal inoculation with H1N1 influenza virus to establish immunity. After 3 weeks, mice were randomized to chow, i.v. feeding of a TPN solution, glutamine-enriched TPN, or glycyl-L-glutamine-enriched TPN. After 4 days of feeding, mice were challenged intranasally with influenza virus and killed at 40 hours to determine viral shedding from the respiratory tract; normal convalescent mice do not shed virus because they possess intact IgA-mediated mechanisms Lymphocytes were isolated from Peyer's patches, the intraepithelial layer, and lamina propria to determine cell yields. RESULTS: Total lymphocyte yield in the Peyer's patches, the intraepithelial layer, and lamina propria decreased with TPN but remained normal with glutamine and glycyl-L-glutamine. Upon challenge, 70% of the mice in the TPN group shed virus in nasal secretions, whereas only 20% of the glutamine-treated group, 18% of glycyl-L-glutamine group and none of the Chow group were virus positive. CONCLUSIONS: L-Glutamine and glycyl-L-glutamine have similar effects on i.v. administered TPN-associated (GALT) atrophy and decreased upper respiratory tract immunity.

Animal Nutritional Physiological Phenomena↗