Biomedical subjects

A Ayala

Publications and source records attributed to A Ayala.

At least 127 records · Page 7Linked to original sources

PubMed1996

Mechanism of immunosuppression in males following trauma-hemorrhage. Critical role of testosterone.

OBJECTIVE: To determine whether male sex steroids contribute to the depression in cell-mediated immunity following trauma-hemorrhage and resuscitation. DESIGN: Two weeks before the induction of soft-tissue trauma (2.5-cm midline laparotomy) and hemorrhagic shock (mean [+/-SEM] blood pressure, 35 +/- 5 mm Hg), male C3H/HeN mice were castrated or sham castrated. Following trauma-hemorrhage, the mice were resuscitated and killed 24 hours thereafter to obtain whole blood and the spleen. RESULTS: Splenocyte proliferation and splenocyte interleukin-2 and interleukin-3 release were significantly depressed in sham-castrated animals after trauma-hemorrhage. In contrast, these variables in castrated mice after trauma-hemorrhage were similar to those in sham-operated animals. Corticosterone plasma levels were significantly elevated in both trauma-hemorrhage groups compared with those in sham-operated mice. Plasma testosterone levels were undetectable in castrated animals and detectable in sham-castrated mice. CONCLUSIONS: Castration before soft-tissue trauma and hemorrhagic shock maintains normal immune function in male mice, but sham-castrated male mice show significant immunodepression. The maintenance of immune function by androgen deficiency does not seem to be related to changes in the release of corticosterone. We conclude that male sex steroids are involved in the immunodepression observed after trauma-hemorrhage. Thus, the use of testosterone-blocking agents following trauma-hemorrhage should prevent the depression of immune functions and decrease the susceptibility to sepsis under those conditions.

Androgens↗

PubMed1996

Depressed splenic function after hemorrhage results from gastrointestinal tract stimulation of hepatic-mediator release. Correction with portacaval shunt.

OBJECTIVE: To determine whether redirecting intestinal blood flow away from the liver via a portacaval shunt would protect distal immune responses in the spleen after hemorrhage. DESIGN: Type C3H/HeN male mice in which a portacaval shunt had been established 2 to 3 weeks before the experiment were bled, their blood pressure was maintained at 35 mm Hg for 1 hour, and then they were resuscitated. Twenty-four hours later, the mice were killed, and mixed and adherent splenocyte cultures were established. The proliferative capacity of splenocytes, the release of interleukin-2 and interleukin-4, and the ability of splenic macrophages to present the antigen, conalbumin, were then determined as indexes of immunocompetence. RESULTS AND CONCLUSIONS: The results indicate that splenocyte proliferation and splenocyte interleukin-2, but not interleukin-4, release were decreased and that splenic macrophage antigen presentation declined after hemorrhage. However, animals in which a portacaval shunt had been established before hemorrhage showed no such changes in their splenocyte or splenic macrophage functions. Thus, the decline of splenic immune responses after hemorrhage seems to be due to mediators released from the gut. Such mediators, in turn, stimulate Kupffer cells to secrete additional agents that produce immunosuppressive exocrine effects on splenic immune functions.

Animals↗

PubMed1996

Prolactin inhibits the increased cytokine gene expression in Kupffer cells following haemorrhage.

Kupffer cells are an important source of proinflammatory cytokines and contribute to the systemic inflammatory response observed following haemorrhagic shock. The systemic release of cytokines, such as TNF-alpha, IL-1 beta, IL-6, etc., has been associated with the decreased host immune and organ dysfunction following hypotension. Studies indicate that anterior pituitary hormone prolactin (PRL) plays an important role in the regulation of lymphocyte proliferation and macrophage function in vivo, as well as in vitro. However, it is not known what effects PRL administration has on Kupffer cells proinflammatory mediator release following haemorrhage. Therefore, it was the aim of this study to determine the effect of in vivo PRL administration on cytokine gene expression in Kupffer cells after haemorrhage. To study this, C3H/HeN male mice were bled to and maintained at a mean arterial pressure of 35 mmHg for 60 minutes, then resuscitated with shed blood, and segregated into two groups: one group was treated with PRL (100 micrograms/25 g body weight subcutaneously) while the other group received saline-vehicles. This was followed with lactated Ringer's solution (2 x the volume of shed blood). Two hours thereafter, the animals were sacrificed, Kupffer cells were isolated and stimulated with or without 10 micrograms/ml LPS for 1 hour. Total RNA was extracted and cytokine mRNA was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results demonstrated that haemorrhage markedly increased the level of mRNA for IL-1 beta, IL-6, TGF-beta and TNF-beta in Kupffer cells. However, in vivo PRL treatment significantly decreased the cytokine gene expression in Kupffer cells following haemorrhage. This indicates that PRL may be useful in blunting the systemic inflammatory response associated with cell and organ depression following shock.

Animals↗

PubMed1996

Enhanced immune responses in females, as opposed to decreased responses in males following haemorrhagic shock and resuscitation.

Although haemorrhagic shock produces immunodepression in both humans and experimental animals, no information is available concerning gender differences in the immune and endocrine response to shock. To study this, male and female (proestrus and diestrus) C3H/HeN mice (25 g body weight) were bled and maintained at a mean arterial blood pressure of 35 +/- 5 mmHg for 1 h and then adequately resuscitated. The animals were killed at 2 h after resuscitation to obtain splenocytes, macrophages (M phi, peritoneal and splenic), as well as whole blood. IL-1 release by M phi, splenocyte proliferative capacity and splenocyte IL-3 release in female mice was significantly increased. Male mice, however, showed decreased release of all interleukins (IL-1, 2, 3, 6) as well as splenocyte proliferative capacity after shock. Plasma corticosterone levels decreased in proestrus female mice, as opposed to increased levels in males following shock. Corticosterone may therefore, be in part responsible for the observed gender differences. To the authors' knowledge, this is the first study which shows that immune responsiveness in female mice is enhanced after haemorrhagic shock, as opposed to decreased responsiveness in males. Thus, unlike males which exhibit increased susceptibility to sepsis/infections, females should be able to better tolerate the deleterious effects of shock.

Animals↗

PubMed1996

Prolactin: a novel and safe immunomodulating hormone for the treatment of immunodepression following severe hemorrhage.

Recent studies have shown that the anterior pituitary hormone prolactin, together with various cytokines, plays an important role in maintaining normal immune responses. Although there is evidence that prolactin may be a significant immunotropic hormone that can counteract the immunosuppressive effects of drugs such as cyclosporine, morphine, or glucocorticoids, it remains unknown whether prolactin administration has any salutary effects on the depressed immune responses following severe hemorrhage. To study this, mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 min, then adequately resuscitated and segregated into two groups. One group received saline-vehicle (hem-SS); animals in the other group were treated with prolactin (hem-PRL) (100 micrograms per 25 g BW, subcutaneously) immediately before resuscitation. Two hours following saline or prolactin injection, splenocytes (SPL) were harvested and assessed for proliferative capacity (PC) and their ability to release IL-2 and IL-3. Supernatant lymphokine levels were determined by bioassay. The proliferative capacity of the splenocytes, as well as their ability to release IL-2 and IL-3, was significantly depressed in the vehicle-treated hemorrhaged animals, compared to shams. Treatment with prolactin restored the depressed splenocyte functions seen after severe hemorrhage. These results support the notion that the immunosuppression following hemorrhage and trauma may be mediated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, our results suggest that the use of prolactin, which did not produce any adverse hemodynamic effects, represents a novel and safe immunomodulating hormone for the treatment of immunodepression following severe blood loss.

Animals↗

PubMed1996

Melatonin administration attenuates depressed immune functions trauma-hemorrhage.

The pineal hormone melatonin has been used in clinical trials in patients suffering from AIDS and also as an adjuvant for cancer therapy. Although melatonin has been reported to have beneficial effects in some animal models of immune dysfunction, it remains unknown whether this hormone has any salutary effects on immunity following soft-tissue trauma and/or major blood loss. To study this, soft-tissue trauma (2.5-cm midline laparotomy) and hemorrhagic shock (arterial BP 35 +/- 5 mm Hg) were induced in C3H/HeN mice. The mice were resuscitated after 90 min of hypotension with the shed blood and lactated Ringer's solution. Treatment with saline, vehicle, or melatonin (10 mg/kg BW) subcutaneously was administered in the evening of the day of surgery and again on the following evening. All animals were sacrificed at 48 hr following trauma-hemorrhage and resuscitation to obtain plasma, splenocytes, as well as splenic and peritoneal macrophages (Mphi). The results indicate that melatonin administration after trauma-hemorrhage significantly improved the depressed immune functions, as evidenced by the restoration of Mphi IL-1 and IL-6 release, as well as significantly improved splenocyte IL-2 and IL-3 release and splenocyte proliferative capacity. No differences in circulating corticosterone levels between vehicle- and melatonin-treated animals were observed. This is the first study to show that melatonin, which is reported to be free of adverse side effects, can be considered a safe and effective therapeutic agent for restoring the depressed immunological function after soft-tissue trauma and hemorrhagic shock.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Melatonin administration following hemorrhagic shock decreases mortality from subsequent septic challenge.

Melatonin administration has been reported to have beneficial effects on immune function in some clinical studies and in several animal models of immune dysfunction. Furthermore, recent studies suggest beneficial effects of melatonin on depressed immune function following trauma-hemorrhage. Nonetheless, it remains unknown whether this hormone has any salutary effects on survival following hemorrhagic shock and subsequent septic challenge. Male C3H/HeN mice were bled to and maintained at a mean arterial blood pressure of 35 +/- 5 mm Hg for 90 min, adequately resuscitated, and 48 hr thereafter subjected to sepsis (cecal ligation and puncture; CLP). Melatonin-treated mice received either short-term treatment on Days 1 and 2 after hemorrhage or continuous treatment throughout the study. Treatment with vehicle (10% ethanol in normal saline) or melatonin (10 mg/kg body weight) was administered daily starting in the evening of the day of hemorrhage/sham-operation. Short-term melatonin administration after hemorrhage significantly improved survival in animals subjected to septic challenge. Continuous melatonin treatment did not improve survival, as compared to vehicle-treated mice subjected to shock and CLP. Moreover, continuous melatonin treatment in sham-operated animals significantly increased mortality compared to short-term-treated and vehicle-treated animals. While the mechanisms of the differential effects of melatonin administration are yet to be clearly defined, this study, nonetheless, demonstrates the salutary effects of short-term melatonin administration in the treatment of immune dysfunction following hemorrhagic shock.

Animals↗

PubMed1996

Oxidative inactivation of tyrosine hydroxylase in substantia nigra of aged rat.

Study of the tyrosine hydroxylase enzyme from substantia nigra and striatum during the aging period of the rat has discovered a significant decrease (55%) of TH activity in substantia nigra between 12 and 24 mo of age. The amount of TH in substantia nigra also decreased (30%) during aging. This loss in TH activity of substantia nigra appears to be produced by the decrease in TH content along with an inactivation process. Our finding showed a significant increase of carbonyl groups in the proteins of rat substantia nigra with aging. A statistically significant increase of carbonyl groups in TH enzyme was found in aged rat brain substantia nigra, indicating that oxidative damage could be the inactivation process that explains the decrease in TH activity found during aging. This hypothesis was corroborated by the fact that when rat striatal homogenate was incubated with hydrogen peroxide, there was a time-dependent decrease in TH activity, which highly correlated with measurements of carbonyl groups content of TH enzyme. The importance of these results may be in their relationship, considering that substantia nigra is preferentially affected in many neurodegenerative disorders.

Aging↗

PubMed1996

The utilization of 5-hydroxyl-2-amino valeric acid as a specific marker of oxidized arginine and proline residues in proteins.

Alteration of cellular proteins by oxidative modification could represent an important mechanism leading to cellular dysdifferentiation and age-related diseases. There is difficulty in testing this hypothesis because of a lack of specific assays that can measure the extent proteins are oxidized in nonpurified tissue preparations. Some methods used to measure carbonyl groups in nonpurified samples have serious limitations because of interference from other sources of carbonyl groups not being a product of oxidation-mediated damage. Oxidation of arginine and proline residues has been reported to produce gamma-glutamyl semialdehyde, which on reduction and acid hydrolysis, was predicted to form 5-hydroxy-2-amino valeric acid (HAVA). In this article we confirm this prediction using a GC/MS/SIM technique, and carry out additional experiments to determine if HAVA may be a useful marker of oxidative damage in proteins. These experiments utilized purified preparations of arginine, proline, histidine, and lysine amino acid homopolymers and six different purified proteins preparations in nonoxidized and oxidized states. Results demonstrate that HAVA compares well with the carbonyl group formation as a specific marker of oxidized protein, and that the GC/MS/SIM technique can detect HAVA reliably to 150 femtomoles per injection. Thus, HAVA as a specific marker of oxidized arginine and proline could prove to be a useful assay in pure and nonpurified samples.

Amino Acids↗

PubMed1996

Comparison of 5-hydroxy-2-amino valeric acid with carbonyl group content as a marker of oxidized protein in human and mouse liver tissues.

Previous studies indicate that 5-hydroxy-2-amino valeric acid (HAVA) is an excellent marker of oxidized arginine and proline in purified proteins. We report here experiments testing the specificity of the HAVA assay technique using the unpurified 100,000 x g supernatant fraction prepared from mice and human liver tissue. Results are compared to carbonyl group analysis on the same tissue samples. Mice at ages 3, 12, and 30 months were exposed to 100% oxygen. Results showed a significant increase of HAVA content in each age group. No significant changes were found in carbonyl group content. Because it has been reported that carbonyl group content increases with age, we applied the HAVA assay to reexamine this question. Using mice of 1 to 30 months of age, we failed to detect any significance difference in either HAVA or carbonyl group content. However, on using human liver samples a significant decrease from age 16 to 40 years and then an increase to 85 years of age was found for both HAVA and carbonyl groups. Liver proteins may be oxidized from hydrogen peroxide produced from the cytochrome P450 detoxification system. This possibility was supported by a significant positive correlation found between HAVA and cytochrome P450 content in 18 human individuals of different ages.

Aging↗

PubMed1996

Optimal delivery of perioperative chemotherapy: preliminary results of a randomized, prospective, comparative trial of preoperative and postoperative chemotherapy for invasive bladder carcinoma.

PURPOSE: We performed a planned interim analysis of a randomized trial comparing initial to postoperative chemotherapy for bladder cancer. The purpose of our analysis was to detect early evidence of survival differences, tolerance to therapy influenced by the sequence of treatment, predictive value of clinical state and influence of methotrexate, vinblastine, doxorubucin and cisplatin (M-VAC) on bladder resectability. MATERIALS AND METHODS: A total of 100 consecutive patients were randomized to receive 2 M-VAC courses before and 3 courses after surgery (group 1) or 5 adjuvant M-VAC courses following cystectomy (group 2). Survival, clinical response, clinical and pathological stage, and toxicity were evaluated in this second timed interim analysis. RESULTS: Of all patients 70% received at least 4 M-VAC courses. Overall survival at 31.7 months (range 1.8 to 87.7) was similar in groups 1 (60%) and 2 (63%), and independent of clinical stage. Preoperative clinical staging accurately identified patients at high risk for recurrence, while 37 of the 48 group 2 patients (77%) were considered at high risk by pathological staging (P3b, P4a, node-positive and unresectable disease). Comparison of pathological stage revealed that 14 of the 51 group 1 patients (28%) achieved stage P0 while only 1 of the 48 group 2 patients (2%) had P0 disease at surgery (p= 0.00043). Disease was unresectable in 3 group 1 (6%) and 8 group 2 patients (17%, p= 0.09). Tolerance to treatment was not significantly different in the 2 study arms. CONCLUSIONS: No survival advantage was noted between neoadjuvant and adjuvant M-VAC in our interim analysis. However, results suggest that M-VAC chemotherapy may be effective in increasing the resectability of localized bladder cancer and may contribute to organ preservation. Clinical stage was a reliable predictor of pathological findings at surgery. Future studies can use clinical staging to determine therapy before surgery for the select stages that we treated. Identification of the subset likely to achieve complete pathological remission will permit the selection of patients for organ preservation strategies.

Adult↗

PubMed1996

Is sepsis-induced apoptosis associated with macrophage dysfunction?

Apoptosis (A O) is a pathological process by which cells undergo a form of inducible nonnecrotic cellular suicide. In vitro studies suggest that changes in the rate of macrophage (Mo) A O may be associated with elevated proinflammatory cytokine secretory capacity, such as interleukin-1 beta (IL-1 beta) (via IL-1 converting enzyme activation). Furthermore, it has been reported that Mo are activated during early (0-4 hours) experimental septic insult to act as sources of proinflammatory cytokines, such as IL-1. However, with the progression of sepsis, these same cells become refractory to further stimulation (appearing dysfunctional). Nonetheless, it remains unknown if this acquired immunosuppression (dysfunction) is associated with an acceleration in macrophage A O. To determine this, male C3H/HeN mice were subjected to sepsis (cecal ligation and puncture, CLP) or sham-CLP and 4 or 24 hours thereafter Mo were isolated from the peritoneum (PMo) and liver (KMo). Macrophage monolayers were lysed either after stimulation with lipopolysaccharide (LPS) (10 microgram/mL, 24 hours) in vitro or immediately (ex vivo) before LPS stimulation and the cytoplasmic cell fraction was retained. The extent of A O was determined using a cell-death enzyme-linked immunosorbent assay, which detects the presence of cytoplasmic oligonucleosomes and changes in the propidium iodide staining intensity. The results indicate that, early after CLP (4 hours) only PMo stimulated with LPS in vitro showed evidence of increasing A O. At 24 hours (late) after the onset of sepsis, the ex vivo extent of A O in PMo was increased but it was decreased in KMo. However, the addition of LPS in vitro results in a marked increase in both septic PMo and KMo A O. This latter result suggests that the inability of Mo to release cytokines in response to stiumulants, such as LPS during late sesis (24 hours), may be because of induciton of accelerated A O in these Mo populations.

Animals↗

PubMed1996

Depressed osteoblast activity and increased osteocyte necrosis after closed bone fracture and hemorrhagic shock.

BACKGROUND: Although bone fracture and hemorrhagic shock are frequent complications in trauma patients, it remains unknown whether hemorrhagic shock after bone fracture produces any deleterious effects on osteoblast function and osteocyte necrosis. METHODS: Sham-operation, closed bone fracture (right tibia) with and without hemorrhagic shock (mean arterial blood pressure 35 +/- 5 mm Hg for 90 minutes followed by fluid resuscitation) were induced in 18 male C3H/HeN mice (25 g body weight) At 72 hours after the experiment, all animals were killed, whole blood was obtained by cardiac puncture, and plasma assayed for circulating levels of osteocalcin. RESULTS: Plasma osteocalcin levels were found to be significantly depressed after closed bone fracture in conjunction with hemorrhagic shock. Closed bone fracture alone increased plasma osteocalcin. Histologic analysis of the fracture sites revealed that hemorrhagic shock after closed bone fracture significantly increased osteocyte necrosis adjacent to the fracture site, when compared to animals with closed bone fracture alone. CONCLUSIONS: These findings suggest that severe hemorrhage after closed bone fracture depresses osteoblast activity and increases osteocyte necrosis, which should compromise fracture healing under those conditions.

Animals↗

PubMed1996

Trauma-induced suppression of antigen presentation and expression of major histocompatibility class II antigen complex in leukocytes.

The immune response to trauma, shock, and/or sepsis appears to exhibit a bimodal response, in which there is an early exaggerated inflammatory response, giving way over time to a state of hyporesponsiveness or immune dysfunction. This state of immune dysfunction is frequently associated with increased infectious complications and/or mortality, seen following shock or trauma. In this article, we present an overview of some of those changes that have been seen with respect to the process of major histocompatibility class II (MHC class II) antigen presentation by macrophage, a key component of the overall host immune response to foreign bacterial and/or fungal pathogens encountered following shock/trauma (with a particular emphasis on hemorrhagic shock as a component of traumatic shock). With respect to the overall process of antigen presentation, defects (dysfunction) are evident not only in models of shock and sepsis, but also in traumatized patients. Studies of the capacity of a monocyte's/macrophage's ability to present antigen indicate that defects can be detected, not only in those steps involved in antigenic processing, but also in MHC class II molecule expression and accessory molecule function (or its inhibition) following shock. Those changes in the macrophage's capacity to process antigen seen during the first 24 h after hemorrhagic shock appear to be associated with the cell's metabolic response to regional hypoxia and/or the shift to proinflammatory mediator release (tumor necrosis factor, interleukin [IL]-1, IL-6, etc.). This initial acute response to shock appears to act as the nidus for chronic anti-inflammatory mediator release (prostaglandin E2, transforming growth factor-beta, IL-10, IL-4, nitric oxide, etc.), which may mediate the sustained depression of the antigen-presenting cell's function.

Animals↗

PubMed1996

Changes in superoxide dismutase activity in liver and lung of old rats.

Superoxide dismutase activity was measured in liver and lung from 3 and 24 month-old rats. Both total SOD and Mn-SOD activity decreased significantly in the liver of old rats. Recent results from our laboratory have indicated that during aging, the activity of Cu/Zn-SOD decreases in rat liver and that there is an accumulation of altered protein. It was also shown that the old Cu/Zn-SOD had one histidine fewer than the young one. In the present study, the immunoprecipitation experiments showed that the amount of immunoprecipitable Mn-SOD from liver of old rats was greater than from young ones, but when amino acid residues were measured in purified young and old Mn-SOD from liver, no change was observed. In lung, no significant age-related differences in total SOD, Cu/Zn-SOD and Mn-SOD activity were found, nor was there accumulation of altered protein during aging.

Aging↗

PubMed1996

The lumbar and femoral bone mineral densities in a normal female Puerto Rican population.

The aim of this study was to establish the reference values of the bone mineral density (BMD) of the lumbar spine and the proximal femur in a normal adult female Puerto Rican population. In the selection of the population, exclusion criteria included diseases, use of drugs and toxic habits (smoking and alcoholism) known to affect bone and mineral metabolism. The study population comprised 131 healthy females, ages 20 to 69 years. Spinal radiographs were taken of women age 60 or more to exclude spinal defects or artifacts. The bone mineral densities were measured using the dual energy X Ray absorptiometer (DEXA, Hologic model 1000). The peak BMD was found in the lumbar spine at the age 30 to 39 years and at the age 20 to 29 years in the femoral neck, trochanter and Ward's triangle. The decrease in BMD from peak values to those at age 60 to 69 years were 18% for the lumbar spine, 16.3% for the femoral neck, 30.1% for the Ward's triangle and 12.4% for the trochanter. The major fall in the BMD was related to the menopause and compares with that of other series. There was no statistical difference from Hologic reference values in a mixed population of the USA.

Absorptiometry, Photon↗

PubMed1996

Platelet activating factor and its role in trauma, shock, and sepsis.

Platelet activating factor (PAF) is a phospholipid mediator released upon stimulation of cells, such as mast cells, basophils, neutrophils, and macrophages, by opsonized agents. This mediator produces a variety of biological effects and acts via specific binding sites present on various cell types. This article briefly reviews the nature of PAF, as well as what is understood about its role in the inflammatory response associated with trauma, shock, and sepsis. Much of what is known of PAF biology and experimental pathophysiology has come from the discovery and subsequent use of selective PAF antagonists. In this respect, several of the PAF antagonists have been examined experimentally and some have been tested clinically in patients with sepsis and septic shock. Experimental and clinical studies suggest that PAF antagonists appear to be effective in cases of severe Gram-negative septic shock. Nonetheless, this mediator may not be a major component involved in the systemic inflammatory response syndrome.

Animals↗

PubMed1996

Immune dysfunction in murine polymicrobial sepsis: mediators, macrophages, lymphocytes and apoptosis.

Despite recent advances in antibiotic therapy, aggressive operative intervention and intravenous hyperalimentation, sepsis, and multiple organ failure are still reported to contribute to significant morbidity and mortality in the surgical intensive care unit. In light of this, it is essential to determine the mechanism underlying the pathophysiology of sepsis so that better therapeutic interventions can be designed. Experimental studies indicate that murine polymicrobial sepsis induces a marked suppression in both lymphocytic and macrophage function associated with decreased cellular adenosine triphosphate levels and increased Ca2+. However, such changes are not detectable until approximately 12 h after the onset of sepsis. Alternatively, early (0-4 h) in sepsis, macrophages from the liver and peritoneum exhibit augmented innate secretion of proinflammatory cytokines, tumor necrosis factor, interleukin (IL)-6, and IL-1, associated with the systemic release of these agents. Sustained release of immunosuppressive agents transforming growth factor-beta, IL-4, IL-10, and PGE2, as well as glucocorticoids, are also observed during sepsis. In this regard, many investigators, including us, have suggested that an agent(s) released as a part of this systemic inflammatory response to sepsis may be responsible for the protracted suppression of immune cell function. Studies examining the effects of these mediators in vitro on various immune cells have shown that many of these agents also have the capacity to induce a process referred to as programmed cell death (PCD) or apoptosis (Ao). We have presented evidence of marked changes in the rate of Ao in immune cells after the onset of sepsis. These data suggest the possibility that mediators released in response to septic insult contribute to the observed changes in immune cell function through the induction of Ao. Inasmuch, understanding the contribution of PCD to the pathophysiology of sepsis, should provide a better basis from which to develop more effective therapy for the septic patient.

Adenosine Triphosphate↗