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Biomedical subjects

E Abraham

Publications and source records attributed to E Abraham.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cytokine expression in Peyer's patches following hemorrhage and resuscitation.

Intestinal dysfunction commonly occurs following hemorrhage and injury and appears to contribute to the development of multiple organ system failure in this setting. In order to examine possible mechanisms leading to intestinal dysfunction following blood loss, we investigated mRNA levels for cytokines with proinflammatory and immunoregulatory properties (interleukin 1 beta (IL-1 beta), IL-6, IL-10, TNF-alpha, TGF-beta, IFN-gamma) as well as mRNA expression for inducible nitric oxide synthase (NOS) over the 3 days following hemorrhage and resuscitation. Significantly increased levels of mRNA for IL-1 beta, IL-10, and IFN-gamma were found among cells isolated from Peyer's patches 3 days following hemorrhage. Amounts of mRNA for inducible NOS were not significantly altered 24 or 72 h after blood loss. In addition to being increased 72 h following hemorrhage, levels of mRNA for IL-10 also were increased 1 and 4 h posthemorrhage. No alterations in cytokine or NOS expression were found 24 h following blood loss. These results demonstrate that significant increases in proinflammatory and immunoregulatory cytokine mRNA levels among cellular populations in Peyer's patches are present at late posthemorrhage time points. These alterations in cytokine expression may contribute to the morphologic, immunologic, and functional changes in the intestines which are present following blood loss and injury.

Amino Acid Oxidoreductases↗
PubMed1994

Effects of therapy with soluble tumour necrosis factor receptor fusion protein on pulmonary cytokine expression and lung injury following haemorrhage and resuscitation.

Acute lung injury frequently develops following haemorrhage, and is characterized by increased proinflammatory cytokine levels and massive neutrophil accumulation in the lung. Blood loss produces rapid increases in tumour necrosis factor-alpha (TNF-alpha) mRNA expression among pulmonary cell populations which precede the development of lung injury. In order to examine the role of TNF-alpha in producing acute inflammatory lung injury, we treated mice following haemorrhage and resuscitation with a TNF antagonist, composed of soluble dimeric human p80 TNF receptor linked to the Fc region of human IgG1 (sTNFR:Fc). Therapy with sTNFR:Fc prevented the post-haemorrhage increases in circulating and pulmonary TNF-alpha levels normally found following blood loss. Administration of sTNFR:Fc also diminished the increase in IL-1 beta, IL-6, TNF-alpha and interferon-gamma (IFN-gamma) mRNA normally found in the lungs following haemorrhage. However, therapy with sTNFR:Fc was not associated with improvement in the histologic parameters of post-haemorrhage lung injury, such as neutrophil infiltration and interstitial oedema. In contrast to the effects of sTNFR:Fc on cytokine mRNA levels among intraparenchymal pulmonary mononuclear cells, such therapy following haemorrhage was associated with increased amounts of mRNA for TNF-alpha among peripheral blood mononuclear cells, as well as increased IFN-gamma titres in serum and bronchoalveolar lavage (BAL) specimens. These results indicate that therapy with sTNFR:Fc in the post-haemorrhage period, although capable of decreasing proinflammatory cytokine expression in the lungs, does not prevent the development of acute lung injury in this setting.

Animals↗
PubMed1994

Hemorrhage and resuscitation induce alterations in cytokine expression and the development of acute lung injury.

Acute pulmonary injury occurs frequently following hemorrhage and injury. In order to better examine the sequence of events leading to lung injury in this setting, we investigated lung histology as well as in vivo mRNA levels for cytokines with proinflammatory and immunoregulatory properties (IL-1 beta, IL-6, IL-10, TNF-alpha, TGF-beta, IFN-gamma) over the 3 days following hemorrhage and resuscitation. Significant increases in mRNA levels for IL-1 beta, IL-6, IL-10, and IFN-gamma, but not TNF-alpha, were present among intraparenchymal pulmonary mononuclear cells obtained 1 and 3 days after hemorrhage. Among alveolar macrophages, TNF-alpha and IL-1 beta mRNA levels were increased 3 days after hemorrhage. Few changes in cytokine mRNA levels, with the exception of TNF-alpha at 3 days after hemorrhage, were present among peripheral blood mononuclear cells. Histologic examination of lungs from hemorrhaged animals showed no alterations 1 day after hemorrhage, but neutrophil and mononuclear cell infiltrates, edema, intra-alveolar hemorrhage, and fibrin generation were present 3 days after hemorrhage. These results suggest that hemorrhage-induced enhancement of proinflammatory cytokine gene transcription may be an important mechanism contributing to the frequent development of acute lung injury following blood loss and injury.

Animals↗
PubMed1994

Anti-transforming growth factor-beta monoclonal antibodies prevent lung injury in hemorrhaged mice.

Acute lung injury, characterized as the adult respiratory distress syndrome (ARDS), is a common clinical occurrence following blood loss and injury. We previously found increased levels of transforming growth factor (TGF)-beta 1 mRNA in murine intraparenchymal mononuclear cells and in alveolar macrophages within 1 h after hemorrhage. Because TGF-beta has potent proinflammatory and immunoregulatory properties, we investigated the effect of blocking TGF-beta with mAb on hemorrhage-induced pathology, cytokine mRNA levels in lungs, as well as survival from pneumonia. Mice treated with anti-TGF-beta mAb showed normal pulmonary histology 3 days after hemorrhage and resuscitation in contrast to the mononuclear and neutrophil infiltrates, intraalveolar hemorrhage, and interstitial edema found in hemorrhaged mice either treated with control antibody or not treated with any antibody. Decreased mRNA levels for IL-1 beta, TNF-alpha, IL-6, IL-10, and IFN-gamma as compared with untreated, hemorrhaged controls were present in intraparenchymal pulmonary mononuclear cells following therapy with anti-TGF-beta. In contrast, therapy with anti-TGF-beta increased mRNA levels for IL-1 beta and TNF-alpha in alveolar macrophages and for TGF-beta in peripheral blood mononuclear cells collected 3 days after hemorrhage. Administration of anti-TGF-beta to hemorrhaged mice did not correct the enhanced susceptibility to Pseudomonas aeruginosa pneumonia that exists after hemorrhage. These results suggest that TGF-beta has an important role in hemorrhage-induced acute lung injury, but does not contribute to the post-hemorrhage depression in pulmonary antibacterial response.

Animals↗
PubMed1994

Effects of therapy with interleukin-1 receptor antagonist on pulmonary cytokine expression following hemorrhage and resuscitation.

Acute lung injury frequently develops following hemorrhage and is characterized by increased proinflammatory cytokine levels and massive neutrophil accumulation in the lung. Blood loss produces rapid increases in IL-1 alpha and IL-1 beta mRNA expression among pulmonary cell populations. To examine the role of IL-1 in producing acute inflammatory lung injury after hemorrhage, we treated mice following hemorrhage and resuscitation with recombinant interleukin-1 receptor antagonist (IL-1Ra), a competitive inhibitor of the actions of IL-1. Therapy with IL-1Ra prevented the posthemorrhage increases in pulmonary TNF-alpha levels normally found after blood loss. Administration of IL-1Ra also diminished the increases in IL-1 beta and IL-6 mRNA levels that occur in the lungs following hemorrhage. However, the amounts of TNF-alpha and IFN-gamma mRNA among intraparenchymal pulmonary mononuclear cells remained elevated after hemorrhage despite therapy with IL-1Ra. These results indicate that therapy with IL-1Ra in the posthemorrhage period is capable of normalizing the expression of some, but not all, of the proinflammatory cytokines whose production among pulmonary cellular populations is increased by blood loss.

Animals↗
PubMed1993

Effects of accidental trauma on cytokine and endotoxin production.

OBJECTIVE: To determine the effects of accidental injury of varying severity on interleukin (IL)-1 alpha, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and endotoxin release. DESIGN: Prospective, multi-unit, longitudinal study. SETTING: Emergency Departments and intensive care units of two university hospitals. PATIENTS: Trauma patients after mild, moderate, and severe injury (Injury Severity Score of < or = 10, 11 to 24, and > or = 25, respectively). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma cytokine and endotoxin concentrations were measured over a 5-day period, starting within 2 hrs of accidental injury. An enzyme-linked immunosorbent assay was used to determine plasma concentrations of IL-1 alpha, IL-6, IL-8, and TNF-alpha. Plasma endotoxin concentrations were measured using a chromogenic limulus amebocyte assay. Preresuscitation samples obtained immediately on arrival in the Emergency Department, and within 2 hrs of injury, demonstrated significant increases of IL-6 and IL-8 concentrations in the severe injury group, in contrast to minimal increases seen after mild or moderate injury. Analysis of serial postresuscitation samples demonstrated rapid increases in IL-6 and IL-8 concentrations within 12 hrs of injury. IL-6 and IL-8 remained increased for 24 hrs after injury, then decreased markedly from their peak values during the next 24 hrs. Increased circulating concentrations of these cytokines continued to be present for > 5 days in the severely injured patients. IL-6 and IL-8 concentrations were only minimally increased in patients 8 and 24 hrs after moderate injury. Endotoxin and IL-1 alpha were not found in any samples, including those samples obtained serially from severely injured patients. No patient at any time point had TNF-alpha concentrations of > 35 pg/mL. CONCLUSIONS: These results demonstrate that severe injury produces rapid, large increases in circulating concentrations of IL-6 and IL-8 that may contribute to the frequent development of the adult respiratory distress syndrome and multiple organ system failure in this clinical setting.

Adult↗
PubMed1993

Sequence of physiologic patterns in surgical septic shock.

OBJECTIVES: Gradual, almost imperceptible transitions occur between localized infection, generalized infection, systemic manifestations of the sepsis syndrome, septic shock, and death. The aim of this study was to describe the sequential pattern of hemodynamic and oxygen transport patterns of survivors and nonsurvivors of septic shock, so as to differentiate primary from secondary and tertiary events, to evaluate possible physiologic mechanisms, and to provide a template to relate the appearance of biochemical mediators to the sequence of physiologic events. DESIGN: Prospective, cohort study. SETTING: University-run county hospital. PATIENTS: A series of 300 consecutive surgical patients with septic shock; 85 survived and 215 died. INTERVENTIONS: We used specific criteria to define stages as: a) early period, the first recorded increase in cardiac output; b) middle period, time of maximal metabolic activity defined as the highest recorded oxygen consumption (VO2); and c) late period, the time of death or recovery. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport variables were measured at frequent intervals throughout the course of septic shock. Beginning with increased cardiac index and oxygen delivery (Do2), which were the earliest observed hemodynamic changes, there were progressive increases in cardiac index, DO2, and VO2. The values of these variables in the survivors were both greater than normal and greater than those values of the nonsurvivors at comparable time periods. These values decreased in the late stage in nonsurvivors. There were early transient reductions in VO2 that preceded the increase in temperature and the decrease in blood pressure in both survivors and nonsurvivors. Although 86% of the septic patients were hyperdynamic, there were transient hypodynamic episodes (defined as cardiac index < 2.5 L/min/m2) in < 10% of the measurements. Transient preterminal hypermetabolic periods occurred in 9% of the nonsurvivors. CONCLUSIONS: Increased cardiac index and DO2 represent compensations for circulatory deficiencies that limit body metabolism, as reflected by inadequate VO2. Survivors have higher cardiac index, DO2, and VO2 values than those values of both the nonsurvivors and normal values. These data suggest that therapy should be directed toward increasing cardiac index to > 5.5 L/min/m2, DO2 to > 1000 mL/min/m2, and VO2 to > 190 mL/min/m2 as therapeutic goals; these supranormal values were empirically determined by the patterns of the survivors. Further studies to describe temporal relationships of biochemical mediators of these physiologic patterns are needed.

Adult↗
PubMed1993

Temporal hemodynamic and oxygen transport patterns in medical patients. Septic shock.

STUDY DESIGN: Because of the gradual insidious transitions between localized infection, generalized infection, and septic shock, it is difficult to compare data of patients in various stages and to differentiate primary from secondary and tertiary events. The aim of the present study was to describe the sequential pattern of hemodynamic and oxygen transport patterns of survivors and nonsurvivors of septic shock in order to evaluate possible physiologic mechanisms and to provide a template to relate the sequence of physiologic events to biochemical mediators. PROCEDURE: A previously described defined protocol was used prospectively to study the sequence of physiologic events using specific criteria to define stages as: (a) early period, the first recorded change in cardiac output; (b) middle period, time of maximal metabolic activity defined as the highest recorded oxygen consumption (VO2); and (c) late period, the time of death or recovery. In addition, three time lines were defined as the first time mean arterial pressure fell below 70 mm Hg, the first time temperature rose above 38 degrees C, and the earliest fall in VO2. Physiologic data were aligned in actual time before or after the time these criteria were met. Invasive hemodynamic and oxygen transport variables were measured with systemic and pulmonary artery catheters; intravascular pressures, arterial and mixed venous gas levels, cardiac output, and derived calculations were made at frequent intervals and keyed to the time of the cardiac output; each set of measurements in turn was keyed to the aforementioned time periods to describe the early, middle, and late periods. RESULTS: Beginning with increased cardiac index and oxygen delivery (DO2) as the early physiologic changes, there were progressive increases in cardiac index, DO2, and VO2 throughout the early and middle periods. They were maintained above the normal range in the late stage of survivors, but fell in the last 16 h in nonsurvivors. These values were greater in survivors than in nonsurvivors throughout. There were early transient reductions in VO2 that preceded the rise in temperature and the fall in mean arterial pressure (MAP). Although 84 percent of the septic patients were hyperdynamic, there were transient hypodynamic episodes defined as cardiac index of less than 2.5 L/min.m2 in approximately 10 percent of the measurements. There were also transient preterminal hypermetabolic periods in about 8 percent of the nonsurvivors. CONCLUSION: We conclude that increased cardiac index and DO2 represent compensations for circulatory inadequacies that limit body metabolism as reflected by VO2. Cardiac index, DO2, and VO2 values of survivors were higher than those of nonsurvivors and normal values. Therapy directed toward increasing cardiac index to supranormal values empirically determined by survivors has been reported to improve outcome. Additional studies to describe temporal relationships of biochemical mediators of these physiologic patterns are needed.

Analysis of Variance↗
PubMed1993

Hemodynamic and oxygen transport monitoring to titrate therapy in septic shock.

Traditionally, shock has been recognized or diagnosed by subjective signs and symptoms, particularly in septic shock, where transition from localized to systemic infection and then to septic shock may be gradual and subtle. Management has been directed toward normalizing these subjective symptoms as well as BP, heart rate, urine output, hematocrit, central venous pressure, and blood gases. The major problem is that restoration to normal values of these secondary aspects of shock do not correct the underlying tissue perfusion defect. The aim of this review is to describe a physiologic mechanistic model based on the concept that uneven vasoconstriction and maldistribution of flow are directly related to tissue hypoxia, oxygen debt, shock, shock-related organ failure, and death; second, to show that titration of therapy to optimal physiologic end-points using hemodynamic and oxygen transport monitoring is a potentially cost-effective therapeutic approach. This physiologic approach is based on the hypotheses that: a) the physiologic patterns of high-risk postoperative and septic survivors are significantly different from septic nonsurvivors; b) tissue perfusion can be evaluated by the sequential patterns of cardiac index, oxygen delivery (DO2), and oxygen consumption (VO2) measurements; c) the observed increased cardiac index and DO2 in the survivors are compensations that improve tissue oxygenation, which is reflected by the VO2 pattern; and d) the supranormal values that were documented in survivors provide objective physiologic criteria for therapeutic goals. The data suggest that a mechanistic analysis of the pathogenesis of shock may be elucidated by temporal patterns of the nonsurvivors' physiologic variables. That is, the predictive indices calculated for each variable quantitatively reflect the relationship of the early changes leading to death or survival. In essence, early changes in those variables statistically related to death may reflect pathogenic mechanisms, while early changes related to survival may be used as a first approximation to therapeutic goals. The application of this approach in prospective, randomized trials has demonstrated that prompt attainment of optimal goals (empirically defined from survivors' patterns) improved outcome in postoperative shock with and without sepsis, as well as in medical sepsis and accidental trauma. Specifically, when the optimal values of cardiac index, DO2, and VO2 used as therapeutic goals were attained in 8 to 12 hrs, there was marked and significant reduction in mortality and morbidity rates. This finding was also confirmed in 12 prospective, controlled trials, four of which were randomized. We conclude that driving septic shock patients into the survivors' patterns improves outcome, as has been shown in other shock syndromes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

T- and B-cell function and their roles in resistance to infection.

Important alterations in T- and B-cell function affecting host defense and resistance to infection are found in critically ill patients and in experimental models of critical illness. In the setting of critical illness, injury, and blood loss, both T and B cells are affected, producing a relatively immunocompromised state where infection is more likely to occur, and where the ability to control the infection is lessened. Alterations in T-cell activation and cytokine production are frequently associated with hemorrhage and trauma. Injury and blood loss result in activation of CD8+ T-cell populations capable of altering bacterial antigen-specific B-cell repertoires and of suppressing the function of other T cells. The production of antibodies directed to bacterial antigens, and required for protection against extracellular bacterial infection, is diminished in models of critical illness, primarily because of disappearance of bacterial antigen-specific B-cell clonal precursors at systemic, pulmonary, and intestinal sites. Correction of the alterations in T- and B-cell function associated with critical illness would be expected to reduce the frequency of nosocomial infections in the ICU. In addition, maintenance of immunocompetence in critically ill patients will permit improved outcome should infection occur.

Animals↗
PubMed1993

Effects of hemorrhage on cytokine gene transcription.

Injury and blood loss are often followed by infection and the rapid development of organ system dysfunction, frequently involving mucosal sites, such as the lung and intestine. To examine possible mechanisms contributing to these conditions, we used semiquantitative polymerase chain reactions to determine cytokine mRNA expression among cellular populations isolated from mucosal and systemic anatomic sites of mice at predetermined time points following 30% blood volume hemorrhage with resuscitation 1 hr later. Within 1 hr after hemorrhage, significant increases were observed in mRNA levels for IL-1 alpha, IL-1 beta, IL-5, and TGF-beta in intraparenchymal pulmonary mononuclear cells. The levels of TGF-beta transcripts among alveolar macrophages were increased 1 hr following blood loss, and increase in IL-1 alpha transcripts was found starting 2 hr posthemorrhage. Cells from Peyer's patches showed significant increases in mRNA levels for IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, and TGF-beta during the 4 hr following hemorrhage. Significant increases in mRNA levels for IL-1 beta, TNF-alpha, and TGF-beta were present within 4 hr of blood loss among cells isolated from mesenteric lymph nodes. The expression of mRNA for most cytokines was not significantly altered in splenocytes or peripheral blood mononuclear cells at any time point following hemorrhage. These experiments demonstrate that blood loss, even if resuscitated, produces significant increases in proinflammatory and immunoregulatory cytokine gene transcription as early as 1 hr following hemorrhage. These posthemorrhage alterations in cytokine mRNA expression were particularly prominent at mucosal sites, suggesting a mechanism for the increased incidence of pulmonary and intestinal involvement in organ system failure following severe blood loss and injury.

Animals↗
PubMed1992

Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-specific pulmonary secretory antibody response.

Secretory IgA (sIgA) present at mucosal surfaces such as the lungs and intestine plays an important role in resistance to infection occurring at these anatomic sites. Because IL-2 and IL-4 can augment B cell proliferation and Ig production, we investigated possible adjuvant effects of these cytokines on bacterial polysaccharide-specific pulmonary sIgA generation. As shown in previous studies, intranasal immunization with liposomes containing bacterial polysaccharide from Aerobacter levanicum and Pseudomonas aeruginosa resulted in increased numbers of bacterial polysaccharide-specific pulmonary plasma cells and sIgA titers, compared with those found in unimmunized mice. Inclusion of IL-2, but not IL-4, into the intranasally administered liposomes further increased titers of bacterial polysaccharide specific sIgA and pulmonary plasma cells. Intranasal vaccination with liposomes containing bacterial polysaccharide and 10 micrograms/kg IL-2 increased bacterial polysaccharide-specific pulmonary plasma cell numbers by more than 80-fold compared with the response in mice immunized with liposomes containing bacterial polysaccharide, but without IL-2. The percentage of pulmonary plasma cells producing antibody to polysaccharide from A. levanicum rose from 0.14% in mice intranasally immunized with liposomes containing only polysaccharide to 4.1% in animals vaccinated with liposomes containing polysaccharide and IL-2. Intranasal immunization with liposomes containing P. aeruginosa polysaccharide and IL-2 significantly reduced mortality from P. aeruginosa pneumonia. These results demonstrate that IL-2 has potent adjuvant effects on bacterial Ag-specific sIgA production in the lungs when included in intranasally administered liposomes.

Adjuvants, Immunologic↗
PubMed1992

Intranasal immunization with bacterial polysaccharide containing liposomes enhances antigen-specific pulmonary secretory antibody response.

Enhancement of bacterial antigen-specific secretory IgA (sIgA) titres in the lungs may enhance resistance to infections, such as pneumonia, occurring at this mucosal surface. To examine this issue, we intranasally administered liposomes containing bacterial polysaccharide antigens from Aerobacter levanicum, Pseudomonas aeruginosa and Streptococcus pneumoniae. In each case, increased titres of bacterial polysaccharide-specific sIgA could be achieved in the lungs following intranasal immunization with antigen encapsulated in liposomes. In comparison with oral immunization, which required high doses of polysaccharide antigen even when coadministered with adjuvant, intranasal administration of liposomes containing polysaccharide antigens achieved a similar pulmonary sIgA response with approximately 1/30 the amount of antigen necessary with oral immunization. In the case of P. aeruginosa, the magnitude of the sIgA response following intranasal immunization was sufficient to significantly reduce mortality from pneumonia produced by this organism. These results demonstrate that liposome-based mucosal immunization strategies can induce increased bacterial polysaccharide antigen-specific sIgA titres in the lung, and reduce susceptibility to pneumonia.

Administration, Intranasal↗
PubMed1992

Effects of granulocyte colony-stimulating factor in modifying mortality from Pseudomonas aeruginosa pneumonia after hemorrhage.

BACKGROUND AND METHODS: Alterations in immune function occurring after hemorrhage and trauma may contribute to the high occurrence rates of nosocomial pneumonia, multiorgan system failure, morbidity, and mortality in this setting. Therapy with granulocyte colony-stimulating factor (G-CSF) can increase neutrophil numbers and function, and enhance resistance to infection in experimental and clinical settings associated with abnormal immune function. To investigate whether treatment with G-CSF could increase resistance to pneumonia after hemorrhage, we bled mice 30% of the blood volume and treated them with various doses of G-CSF, starting either immediately or 2 days after hemorrhage. Pseudomonas aeruginosa pneumonia was induced by the intratracheal instillation of 2 x 10(7) colony-forming units of P. aeruginosa 4 days after blood loss, and mortality was assessed over the next 7 days. RESULTS: Treatment of mice with 100 or 500 micrograms/kg/day G-CSF, but not with 50 micrograms/kg/day, resulted in significant increases in the numbers of circulating polymorphonuclear cells. Platelet counts significantly decreased in mice given 500 micrograms/kg/day G-CSF. Mice given 100 micrograms/kg/day G-CSF starting 2 days after blood loss had improved outcome compared with vehicle-treated controls (38% survival rate in the G-CSF treated group vs. 8% in controls, p less than .05). There also was a trend toward an improved survival rate in mice treated with 50 micrograms/kg/day G-CSF for 4 days after hemorrhage (46% survival rate in G-CSF treated vs. 17% in controls). CONCLUSIONS: G-CSF prophylactically administered after hemorrhage can improve survival from pneumonia due to P. aeruginosa. However, the protection afforded by G-CSF was highly dependent on the dosing schedule used.

Analysis of Variance↗
PubMed1992

Effects of haemorrhage on bacterial antigen specific pulmonary plasma cell function.

Nosocomial pneumonia is frequent after haemorrhage and trauma, and often contributes to multiple organ system failure, morbidity and mortality in this setting. Although the percentages and numbers of bacterial polysaccharide antigen-specific pulmonary B cell clonal precursors are markedly decreased after haemorrhage, the effects of haemorrhage on pulmonary plasma cells actually producing antibody to these antigens are unknown. To investigate this question, the numbers of intraparenchymal pulmonary plasma cells producing antibody against the bacterial polysaccharide antigen levan (from Aerobacter levanicum) as well as bacterial antigen specific secretory IgA (sIgA) titres in the lungs were determined at various time points after 30% blood volume haemorrhage. Reduced numbers of bacterial antigen specific pulmonary plasma cells were found for more than 21 days following haemorrhage. An almost complete disappearance from the lungs of levan specific plasma cells occurred between 3 and 21 days after blood loss. Titres of bacterial antigen specific sIgA in the lungs were decreased starting at 3 days post-haemorrhage and remained significantly depressed for more than 35 days after blood loss. These results demonstrate that haemorrhage produces profound and long-lasting suppression in bacterial antigen-specific pulmonary plasma cell function. Because these effects do not occur immediately post-haemorrhage, immunization techniques able to enhance bacterial antigen specific sIgA titres at pulmonary surfaces may be able to increase resistance to nosocomial pneumonia if administered shortly after injury and blood loss.

Animals↗