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E Faist

Publications and source records attributed to E Faist.

At least 55 records · Page 3Linked to original sources
PubMed1993

Regulation of acute phase response after cardiopulmonary bypass by immunomodulation.

The object of this prospective, randomized trial was to study the dysregulation effects of cardiopulmonary bypass on the synthesis pattern of interleukin-1, tumor necrosis factor, and interleukin-6, which have been identified as the key mediators of acute phase response. In addition, the counterregulation achieved by administration of indomethacin, which blocks the downregulating mediator prostaglandin E2, or indomethacin combined with thymopentin, which enhances T-lymphocytic reactivity, was investigated. Sixty patients who had undergone open heart operations were included in the study. These patients were divided into three groups: group A (n = 20) received both indomethacin and thymopentin, and group C (n = 20) served as control. In control patients interleukin-1 and tumor necrosis factor synthesis were suppressed postoperatively. This effect was significantly counteracted by indomethacin with no further improvement by adding thymopentin. Interleukin-6 synthesis increased in all groups. Although indomethacin treatment alone had little effect on this phenomenon, additional administration of thymopentin significantly reduced elevated interleukin-6 synthesis. Corresponding differences in clinical outcome could not be detected due to small patient numbers. This study was, however, able to demonstrate that an immunomodulatory therapy can influence alterations in immune mechanisms after cardiopulmonary bypass.

Acute-Phase Reaction↗
PubMed1993

Alterations of cell-mediated immune response following cardiac surgery.

Nosocomial infections in patients following cardiac surgery are frequently associated with opportunistic microorganisms indicating a dysregulation of cell-mediated immune response. The objective of this prospective randomized trial, therefore, was to investigate the mechanisms of dysregulation and the counterregulatory effects of immunomodulation. Twenty patients underwent conventional postoperative therapy, another 20 patients received indomethacin, which inhibits synthesis of the down-regulating mediator prostaglandin E2, and a further 20 patients were given thymopentin in addition to indomethacin, thereby augmenting activation and differentiation of the T-lymphocytes. The immunologic parameters studied included T-lymphocytes and monocytes as well as interleucin (IL)-1 and IL-6 synthesis by monocytes, and IL-2 and IL-6 synthesis by T-lymphocytes. Following cardiac surgery a significant, persistent reduction of T-lymphocytes and IL-2 synthesis as well as significant monocytosis could be observed. Indomethacin treatment resulted in a normalization of the cellular imbalance at the end of the first postoperative week, but IL-2 synthesis remained significantly reduced during the entire observation period. Conversely, with combined indomethacin and thymopentin treatment restoration of cellular distribution as well as protection of IL-2 synthesis could be achieved. These results indicate a quantitative and functional impairment of the forward regulation of cell-mediated immunity. It was shown for the first time that combined indomethacin and thymopentin treatment could successfully counteract these immunomechanistic alterations.

Aged↗
PubMed1993

Inadequate interleukin-2 synthesis and interleukin-2 messenger expression following thermal and mechanical trauma in humans is caused by defective transmembrane signalling.

The study was performed to further elucidate the mechanisms of dysfunctional T-cell activation following extensive burn and mechanical injuries. The major regulatory level of interleukin-2 (IL-2) release under stressful conditions was determined via parallel analysis of IL-2 messenger RNA (mRNA) expression and IL-2 protein synthesis in mitogen-stimulated peripheral blood mononuclear cell (PBMCs) cultures on consecutive days postinjury. Furthermore, we wanted to scrutinize if inadequate lymphokine production after trauma is possibly a result of defective transduction of extracellular signals to the T-cell nucleus. Fourteen patients (11 men, 3 women, average age 38 +/- 6 years, Injury Severity Score 34 +/- 2) were included in the study. The PBMCs were isolated on days 1, 3, 5, 7, and 10 and stimulated either with the mitogen phytohemagglutinin (PHA) alone or in combination with the protein kinase C (PKC) activator phorbol myristate acetate (PMA). The protein release was examined via bioassay (human con-A blasts) from the supernatants, and the cellular RNA was indicated by radioactive hybridization with the specific complementary DNA (cDNA) after Northern blotting. The IL-2 protein synthesis generated in PHA-stimulated PBMC cultures following trauma, compared with that in controls (0.62 +/- 0.04 U/mL) was persistently and significantly depressed during the observation time with a 57% inhibition on day 10-identical with that on day 1. The Northern blot analysis of IL-2 mRNA expression in the lysates of PHA-stimulated cell cultures after trauma could not detect any mRNA signal for IL-2, in contrast to the control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Mechanisms of cytokine cascade activation in patients with sepsis: normal cytokine transcription despite reduced CD14 receptor expression.

BACKGROUND: Lipopolysaccharide causes activation of monocytes/macrophages with excessive secretion of cytokines resulting in hypotension and shock in patients with sepsis. Lipopolysaccharide may induce these responses by interacting with lipopolysaccharide-binding protein and then binding to the cell surface protein CD14 or by acting directly with CD11-CD18 on monocytes/macrophages. The role of CD14 and CD11-CD18 in the activation of macrophages with enhanced cytokine transcription in patients with septic shock remains to be determined. METHODS: To study this, heparinized blood was obtained from 16 patients with septic shock on days 0, 1, 3, 5, 7, and 10 and compared with 20 control patients. The expression of CD14 and CD11b on monocytes in whole blood was measured by direct immunofluorescence and flow cytometry. Moreover, whole blood was stimulated with lipopolysaccharide (1 microgram/ml) for 0, 1, 2, 4, 8, and 24 hours, and messenger RNA expression for tumor necrosis factor-alpha, interleukin-beta (IL-1 beta), and IL-6 was determined on isolated peripheral blood mononuclear cells with Northern blot analysis. RESULTS: Both CD14 expression and receptor density on monocytes from whole blood were markedly suppressed (-63% on day 3; p < 0.05) in the septic group compared with controls. Although CD11b expression was also decreased (-24% on day 1; p < 0.05), receptor density on monocytes was slightly increased in the septic group in comparison with the control group. Kinetics and intensity of messenger RNA expression for tumor necrosis factor-alpha, IL-1 beta, and IL-6 were similar in both groups. CONCLUSIONS: These data indicate that in patients with septic shock, lipopolysaccharide-mediated signaling and cytokine transcription are unchanged despite a significant reduction of CD14 expression and density on monocytes. Thus, lipopolysaccharide-induced activation of monocytes from patients with sepsis may occur through direct binding of lipopolysaccharide to the CD11-CD18 complex or other lipopolysaccharide receptors, whereas binding of the lipopolysaccharide-lipopolysaccharide-binding protein complex to the CD14 receptor may not play a pivotal role in sepsis.

Adult↗
PubMed1993

The influence of major trauma on the regulatory levels of interleukin-1 (IL-1) and IL-2 in human mononuclear leukocytes.

The monokine Interleukin-1 (IL-1) and the lymphokine IL-2 are playing a crucial role within the course of an intact cell mediated immune response (CMI). It was the objective of this study to further elucidate the cytokine associate mechanisms of dysfunctional T-cell activation following major burn and mechanical trauma. Via comparative analysis of mRNA expression and protein release the major regulatory levels of IL-1 and IL-2 release under stressful conditions were to be determined in mitogen respectively LPS stimulated PBMC (peripheral blood mononuclear cells) cultures on consecutive days (D) 1, 3, 5, 7 and 10 post injury. Further, we wanted to scrutinize if inadequate IL-2 production post-trauma is possible due to a defective transduction of extracellular signals to the T-cell nucleus. In order to answer this question IL-2 mRNA expression and IL-2 protein releases were determined in PBMC cultures using the phosphokinase C (PKC) activator phorbol ester (PMA) as a costimulus together with PHA. When analyzing the cumulative data for IL-1 beta we saw until D 5 post-trauma a considerable impairment of the protein release in LPS stimulated PBMC cultures and recovery thereafter. In only a few individual PBMC cultures we saw a concurrence between the IL-1 beta mRNA signal intensity and the protein production. In the majority of the autoradiographies analyzed, the mRNA expression for IL-1 beta was considerably more distinct compared to controls while the corresponding protein release values were on control level or below. These results implicate that the suppression of IL-1 beta post-trauma is regulated mainly on a posttranscriptional level. Since Prostaglandin E2 (PGE2) has been found to have a vigorous impact on the IL-1 beta synthesis on the translational level, we assume that the high PGE2 levels post-trauma inhibit--via cAMP--sufficient IL-1 beta synthesis on the posttranscriptional level. IL-2 protein synthesis as well as mRNA expression in mitogen (PHA) stimulated PBMC cultures following trauma, was persistently and significantly depressed compared to controls during the time of observation. The addition of PMA as a costimulus to PHA, could induce very distinct mRNA signals for IL-2 with a signal intensity which was comparable to that found in the cells of healthy controls. Also the quantity of IL-2 protein release in the vast majority of all patients PBMC cultures following PHA/PMA induction was within the control range.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation.

The objectives of this prospective randomized trial were to quantify immunosuppressive effects of cardiopulmonary bypass, to identify mechanisms responsible for postoperative immunosuppression, and to investigate the effects of immunomodulatory intervention on these mechanisms. Sixty patients were studied after cardiopulmonary bypass. Immunomodulatory therapy consisted of the cyclooxygenase inhibitor indomethacin, which blocks the downregulating agent prostaglandin E2, and thymopentin, which enhances T-lymphocytic activity. Twenty patients each received indomethacin either alone or combined with thymopentin. Twenty patients served as the control population. Our in vitro studies showed a decrease of CD4+ helper/inducer T cells and interleukin-2 receptor expression on T lymphocytes, while CD8+ suppressor/cytotoxic T cells and monocytes increased. Additionally, a depression of interleukin-1 and interleukin-2 synthesis as well as concurrent low gamma-interferon serum concentrations could be documented. These results indicate a downregulation of cell-mediated immune response. As an in vivo correlate of the immunomechanistic alterations, patients demonstrated an impaired delayed-type hypersensitivity response to an antigen skin test battery. These changes in immunoreactivity could be successfully counteracted by the combined immunomodulatory regimen, whereas sole indomethacin treatment could only partially restore depressed host defense parameters. With this study we could demonstrate for the first time that human lymphocytic interleukin-2 synthesis, which represents the key event among forward regulatory immune mechanisms, can be protected via in vivo immunoaugmentatory therapy and that this therapy can successfully counteract immunosuppressive effects of cardiopulmonary bypass.

Aged↗
PubMed1993

[Immunologic monitoring after severe trauma].

Trauma, burn injury, and major surgery lead to severe suppression of the immune system with an increased susceptibility to septic complications. Therefore, the monitoring of essential immune functions in the early and late post-traumatic course may permit trauma patients with an increased risk for infectious complications to be identified. Most functions of the specific and non-specific immune system can be determined with ELISA, RIA, or other immunological techniques. However, only a small number of these techniques demonstrate an acceptable sensitivity and specificity for infectious complications. Moreover, the techniques used in daily monitoring should be simple, reproducible and not expensive with regard to materials. For immunological monitoring we suggest two scoring systems (ISS; APACHE II), biochemical parameters (elastase, neopterin, CRP, lactate), and interleukin-6 plasma levels. The clinical relevance of this monitoring must be proven in clinical studies.

Burns↗
PubMed1992

Changes in lymphocyte subsets and mitogen responsiveness following open-heart surgery and possible therapeutic approaches.

Septic multi-organ failure represents a common cause for operative mortality following open-heart surgery. One major reason might be the depression of cell-mediated immunity. The purpose of this prospective randomized trial was to quantify and specify the effects of open-heart surgery on cell-mediated immune mechanisms. In addition, the immunorestorative potential of a combined immunomodulatory therapy with the cyclooxygenase inhibitor indomethacin and the thymomimetic substance Thymopentin versus single drug administration of indomethacin was investigated. Twenty patients were given indomethacin for the first 5 postoperative days (group A). Another 20 patients also received Thymopentin perioperatively and on the second and fourth postoperative days (group B), while 20 patients underwent conventional therapy (group C). Cell-mediated immune response was quantified in vitro by measuring CD3+ T-lymphocytes and their subsets, CD4+ T-helper and CD8+ T-suppressor cells. Lymphocyte responsiveness to a specific (Antigen-Cocktail) and non-specific mitogen (phytohemagglutinin) provided information about the quality of cell-mediated immune response. On the first postoperative day CD3+ T-lymphocyte counts and Antigen-Cocktail-induced lymphocyte proliferation decreased significantly in all groups. The number of CD4+ T-Helper cells fell significantly only in groups A and C, while the decrease in group B was not statistically significant; the same applied to phytohemagglutinin-induced lymphocyte response. The CD4+/CD8+ ratio was significantly depressed only in group C, decreased slightly in group A and did not change as compared to baseline values in group B. All investigated parameters remained significantly depressed until the seventh postoperative day in group C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Functional analysis of monocyte activity through synthesis patterns of proinflammatory cytokines and neopterin in patients in surgical intensive care.

This study was designed to further differentiate monocyte behavior in critically ill patients with operative or accidental trauma. The patient population studied consisted of 39 patients (17 patients undergoing elective surgery [ES], seven patients with major multiple injuries [MI], and 15 patients in an acute septic state [S]). Immunologic parameters assessed included monocyte phenotyping with the monoclonal antibody LeuM3, measurement of the cytokines interleukin (IL)-1, IL-6, and IL-8 in lipopolysaccharide-stimulated in vitro cultures of mononuclear leukocytes (PBMCs), and determination of neopterin in gamma-interferon-stimulated in vitro cultures and corresponding serum samples. Serum neopterin levels were very high in S patients (89.0 nmol/L; p less than 0.05) compared with control values (4.6 nmol/L), with a rise to 16.4 nmol/L in ES patients on day 7 and 13.4 nmol/L in MI patients on day 7. The concentrations of gamma-interferon-induced neopterin in the supernatants of the PBMC cultures were elevated in all patient groups. Severe impairment of IL-1 synthesis was seen in MI and S patients. IL-8 synthesis (818 +/- 150 units/ml, control value) was also suppressed (p less than 0.05) in MI patients; the values were 135 +/- 65 units/ml on day 1,231 +/- 110 units/ml on day 3,347 +/- 131 units/ml on day 7, and 355 +/- 107 units/ml in S patients. The kinetic patterns of synthesis were comparable for IL-1 and IL-8 in all patient groups. Lipopolysaccharide-induced IL-6 synthesis (9.4 +/- 1.5 x 10(3) units/ml, control value) was significantly elevated in the PBMC cultures of all patient groups, with the exception of the early phase after accidental trauma. Maximum amounts of IL-6 synthesis after surgery were 19.6 +/- 7 x 10(3) units/ml in S patients and 19.0 +/- 2.2 x 10(3) units/ml in ES patients. These results demonstrate (1) the impairment of the functional capacity of circulating monocytes and (2) that the degree of functional impairment is proportional to the severity of the injury.

Adolescent↗
PubMed1991

Immunomodulatory therapy with thymopentin and indomethacin. Successful restoration of interleukin-2 synthesis in patients undergoing major surgery.

Prostaglandin E2 (PGE2)-mediated monocyte (M phi) suppressor activity and inadequate T-helper cell function represent the mechanistic keystones of trauma-induced impairment of cell-mediated immunity (CMI). In a prospective randomized trial, the immunorestorative potential of a combined therapy with the thymomimetic substance Thymopentin (TP-5; Timunox, Cilag GMBH, Sulzbach, FRG) and the cyclooxygenase inhibitor indomethacin (Indo) in 60 patients (mean age, 63 +/- 2 years) undergoing open heart surgery was studied. Perioperative immunologic screening was carried out on days -2, 3, 1, 5, and 7 and included the in vivo delayed type hypersensitivity (DTH) skin response, phenotyping for peripheral blood mononuclear cell (PBMC)-specific and nonspecific induction of lymphoproliferative responses, in vitro interleukin-2 (IL-2) synthesis, as well as the serum concentration of D-erythro-Neopterin (NPT) and of gamma interferon (gamma-IFN). The study protocol comprised three groups (n = 20): PA (Indo 150 mg administered intravenously on days 0 to 5), PB (TP-5 administered subcutaneously on days 0, 2, 4, and Indo), and PC (control). In contrast to PC, significant immunorestoration could be demonstrated in PB, as DTH scores on day 7, as well as proliferative responses in cell cultures were not depressed after operation (p less than 0.05). Cell-surface receptor expression for the CD3+, CD4+, and IL-2 receptor-positive (IL-2R+) lymphocyte subpopulations following surgery was reduced to 75% of baseline values in PC, while in PB, receptor protection for CD4+ and IL-2R+ subpopulations (more than 15% above baseline) was observed. Interleukin-2 synthesis (average baseline value, 0.7 + 0.08 U/mL) in cell cultures of PC was massively suppressed, with lymphokine concentrations in the supernatants never more than 0.27 +/- 0.05 U/mL. In PA cultures, IL-2 synthesis was impaired as well but not as precipitously as in PC. In contrast, in PB cultures, the average IL-2 production on consecutive postoperative days was never below baseline values. This study clearly demonstrates that the combined Indo/TP-5 therapy is superior to single Indo administration and can adequately preserve and/or restore intact M phi T-cell interaction and thus appears to be a feasible approach to maintain normal host defense activity in traumatized individuals.

Adjuvants, Immunologic↗
PubMed1990

Kinetics of interleukin-2 and interleukin-6 synthesis following major mechanical trauma.

Although it is known that mitogen-induced lymphocyte proliferation and interleukin-2 (IL-2) synthesis are depressed following mechanical trauma, it is not known whether these defects are due to high levels of circulating prostaglandin E2 released by macrophages, suppressor T-lymphocytes, and serum suppressive factors or due to intracellular defects in T-lymphocytes. Moreover, the kinetic of interleukin-6 (IL-6), a new multifunctional cytokine, following trauma is not known. To study this, highly purified T-cell cultures were prepared from 21 patients with major mechanical trauma on Days 3, 7, 10, 14, and 21 post-trauma and assayed for proliferative response to phytohemagglutinin, IL-2, and IL-6 synthesis. T-lymphocyte proliferation of patients was unaltered on all days post-trauma compared to that of healthy controls. Interleukin-2 synthesis of patients showed a significant (P less than 0.01) reduction ranging from 23% of control values on Day 3 to 40% on Day 21. Interleukin-6 synthesis in contrast was markedly increased (P less than 0.05) in the patient group on all days up to sixfold (Day 3) with a tendency toward normalization on Day 21. High levels of IL-6 correlated with the appearance of infectious complications in the post-traumatic course. These data indicate that the alterations in T-cell proliferation and IL-2 synthesis following major injury found in earlier studies are caused by different suppressor mechanisms. While T-cell proliferation is only decreased by extracellular components, IL-2 synthesis is suppressed mainly by an intracellular defect. The role of highly increased IL-6 levels and its effect on the immune response are so far unknown.

Adolescent↗
PubMed1990

Immunoprotective effects of cyclooxygenase inhibition in patients with major surgical trauma.

Dysfunctional monocytes (M phi), exerting their inhibitory functions via prostaglandin E2 (PGE2), have been implicated in the depression of immune responses following major surgical, accidental, and burn trauma. A randomized prospective study of the PG-synthetase inhibitor indomethacin (Indo) was performed in 43 patients undergoing major surgical procedures, to evaluate its efficacy in correcting postoperative abnormalities of the cell-mediated immune system (CMI) and preventing infectious morbidity and mortality. Patients, following gastrectomy (GX) or reconstruction of the abdominal aorta (AG), in the treated group (PIndo), received 100 mg IV of Indo 6 hours postoperatively and 3 x 50 mg IV Indo over 24 hours on postoperative days (D) 1,2,3,4. The rate of infectious complications was recorded. Parameters of CMI evaluated preoperatively (D0) and on D1,D3,D5,D7 were: Delayed type hypersensitivity (DTH) response to recall antigens, mitogen-induced lymphocyte proliferation (LP), interleukin 2 (IL-2) synthesis, and phenotyping of mononuclear blood leukocytes (PBMC's) with the monoclonal antibodies for CD3+, CD4+, IL-2 receptor (IL-2R)+ and LeuM3+ receptor sites. In contrast to the group of untreated patients (Pc), PIndo did not show a depression of their preoperative DTH responses, and they also showed a lower rate of early opportunistic infections. The in vitro test of CMI revealed that there was a higher LP capacity in PBMC's of PIndo (p less than 0.05); the postoperative profile of IL-2 synthesis was not statistically different between the groups. Indomethacin administration resulted in a considerable alleviation of postoperative monocytosis (p less than 0.05) and in a protective effect on lymphocyte receptor expression of CD3+, CD4+, and IL-2R+ cells. From these data it is concluded that in vivo cyclooxygenase inhibition may be useful to prevent impairment of CMI, a crucial predisposing factor of the high susceptibility to postoperative infection.

Aged↗
PubMed1989

Dynamics of immunoglobulin synthesis after major trauma. Influence of recombinant lymphokines.

Major mechanical trauma causes a severe suppression of B-cell differentiation and IgM synthesis in mononuclear leukocyte cultures. In this study the effect of recombinant lymphokines and physiologic T-cell supernatants on B-cell differentiation was investigated. The influence of potentially suppressing monocytes and positive regulatory T-lymphocytes was eliminated using purified B-cell cultures. Antigen-induced IgM synthesis was reduced on all days following trauma. Addition of recombinant interleukin 2 or T-cell supernatant enhanced but did not restore IgM synthesis. Although recombinant interleukin 4 and recombinant interferon gamma had a suppressive effect on IgM synthesis in controls, both lymphokines were ineffective in the patients' IgM synthesis. Spontaneous IgG production in patients was dramatically elevated, and the addition of lymphokines did not show any enhancing effect in patients. These results demonstrate that the IgM/IgG shift observed in peripheral blood mononuclear cell cultures also exists in purified B-cell cultures. Interleukin 2 partially restored suppressed IgM synthesis, while interleukin 4 and interferon gamma were ineffective in patients' B-cell differentiation. Interleukin 2 was the most effective lymphokine for the induction of Ig synthesis. These results lead us to conclude that the altered B-cell metabolism might also be responsible for the suppression of humoral immunity following trauma.

Adolescent↗
PubMed1989

Terminal B-cell maturation and immunoglobulin (Ig) synthesis in vitro in patients with major injury.

This study evaluated B-lymphocyte function in 30 patients following major trauma with frequent screening over a period of 21 days post-trauma. Peripheral blood mononuclear cells (PBMC) were phenotyped with monoclonal antibodies and in vitro B-cell function was tested both for unstimulated cells (spontaneous) and following stimulation with pokeweed mitogen (PWM). The capacity for terminal B-cell maturation into plasma cells was assessed by the number of cells bearing cytoplasmic immunoglobulin (CIg+). Although the number of circulating B cells in the trauma patients was not decreased following injury (12 +/- 2%), the number of CIg+ cells was significantly decreased (0.2 +/- 0.1 to 3.0 +/- 1.5) compared to controls (5 +/- 1) up to 21 days post-trauma (p less than or equal to 0.01). Spontaneous B-cell synthesis of IgA, IgM, and IgG was significantly depressed on day 1, but IgA was within normal range (159 +/- 30 ng/ml) by day 3, and IgA levels were supranormal (118 to 300% of control) on days 5-10 before returning to normal on days 14 to 21. Synthesis of IgG was 100 +/- 20 ng/ml on day 3 (control, 165 +/- 31 ng/ml), and IgG levels were supranormal (+45 to +139%) thereafter. On the other hand, IgM synthesis was decreased on all days studied (120 +/- 35 to 220 +/- 70 ng/ml) compared to controls (366 +/- 105 ng/ml). Synthesis of all Ig subclasses in PWM cultures followed a similar pattern. There was a marked monocytosis (30 +/- 2% LeuM3 + PBMC's) compared to control values (13 +/- 2% LeuM3+ PBMC's).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Alteration of monocyte function following major injury.

The macrophage exerts its stimulatory and regulatory functions within the specific immune response via the interleukin 1 (IL-1) and prostaglandin E2 (PGE2), respectively. In a screening study of macrophage-related variables following injury, a total of 58 patients (mean age, 32 years; mean injury Severity Score, 38), macrophagic phenotyping with the monoclonal antibody Leu M3 and serial measuring of the antagonistic monokines IL-1 and PGE2 and of the macrophage-activating lymphokine interferon gamma were carried out on posttrauma days 0, 1, 3, 5, 7, 10, 14, and 21. The posttraumatic course was characterized by significant monocytosis, showing a peak value of 32% of Leu M3-positive cells compared with 15% of these cells in normal control subjects. During the posttrauma course, the macrophagic PGE2 output was significantly elevated up to eightfold on days 5 and 7 compared with that of control subjects (0.441 +/- 0.14 ng/mL vs 0.052 +/- 0.01 ng/mL). Conversely, macrophagic IL-1 synthesis was significantly suppressed until day 10. Levels of interferon gamma were suppressed to a significant degree during the two-day observation period, with a trend to slow recovery at the end of week 3. These data suggest that a negative regulatory macrophagic function may be the event initiating posttraumatic immunosuppression. To restore impaired macrophagic T-helper cell interaction, cyclo-oxygenase inhibition and substitution of interferon gamma may be useful to potentiate facilitatory macrophagic function and to block inhibitory macrophagic activity.

Adolescent↗