Biomedical subjects

R Zellweger

Publications and source records attributed to R Zellweger.

At least 19 recordsLinked to original sources

PubMed2000

Transfusion of washed and centrifuged shed RBCs during maxillofacial surgery affects cytokine concentrations.

BACKGROUND: In patients undergoing elective maxillofacial surgery, hyperthermic reactions have been observed after the transfusion of autologous washed and centrifuged shed blood. It was the aim of this study to correlate the clinical features with changes in cytokine levels. STUDY DESIGN AND METHODS: In 24 consecutive patients, TNFalpha, IL-1, and IL-6 levels were determined in washed and centrifuged shed RBCs (CS RBCs) and in the patient's serum before, as well as 15 and 120 minutes after transfusion. At the same time, blood was drawn for culture. Patients in whom whole blood was saved through the use of acute normovolemic hemodilution served as a control group (n = 6). RESULTS: After the transfusion of CS RBCs, patients had not only elevated cytokine levels but also transient bacteremia involving the pathogens previously detected in CS RBCs. No rise in body temperature occurred. CONCLUSION: In the light of these results, the use of CS RBCs in patients undergoing maxillofacial surgery should be restricted to those patients with no primary bacterial contamination.

Adolescent↗

PubMed2000

Richter's hernia and Sir Frederick Treves: an original clinical experience, review, and historical overview.

OBJECTIVE: To describe the clinical recognition, pathology, and management of Richter's hernia and to review the relevant literature of the past 400 years. SUMMARY BACKGROUND DATA: The earliest known reported case of Richter's hernia occurred in 1598 and was described by Fabricius Hildanus. The first scientific description of this particular hernia was given by August Gottlob Richter in 1778, who presented it as "the small rupture." In 1887, Sir Frederick Treves gave an excellent overview on the topic and proposed the title "Richter's hernia." To his work-a cornerstone to modern understanding-hardly any new aspects can be added today. Since then, only occasional case reports or small series of retrospectively collected Richter's hernias have been published. METHODS: The authors draw on their experience with 18 prospectively collected cases treated in the ICRC Lopiding Hospital for War Surgery in northern Kenya between February and December 1998 and review the relevant literature of the past 400 years. RESULTS: The classic features of Richter's hernia were confirmed in all case studies of patients: only part of the circumference of the bowel is entrapped and strangulated in the hernial orifice. The involved segment may rapidly pass into gangrene, yet signs of intestinal obstruction are often absent. The death rate in the authors' collective was 17%. CONCLUSION: Richter's hernia is a deceptive entity whose high death rate can be reduced by accurate diagnosis and early surgery. Considering the increasing incidence at laparoscope insertion sites, awareness of this special type of hernia with its misleading clinical appearance is important and of general interest.

Adult↗

PubMed2000

Effect of naloxone on immune responses after hemorrhagic shock.

OBJECTIVE: To determine whether naloxone administration after hemorrhagic shock has any beneficial or deleterious effect on immune responses. BACKGROUND DATA: Hemorrhagic shock is known to produce immunodepression in both humans and experimental animals. Although studies suggest that endogenous opioids play a role in immune regulation in adverse circulatory conditions, it remains controversial whether these opioids exert beneficial or detrimental effects on immunity after shock. Moreover, little information is available concerning the effects of opioid receptor blockade using naloxone on cell-mediated immunity and endocrine responses after shock. METHODS: Male C3H/HeN mice (25 g) were bled to and maintained at a mean arterial blood pressure of 35+/-5 mm Hg for 1 hr. The shed blood was then returned along with lactated Ringer's solution (two times the shed blood volume) to provide fluid resuscitation. The animals were randomized to receive either naloxone (1 mg/kg i.v.) or an equal volume of vehicle (saline) after the shed blood was returned, i.e., immediately before crystalloid resuscitation, and were killed at 2 hrs after resuscitation to obtain splenocytes, macrophages (peritoneal and splenic), and blood. MEASUREMENTS AND MAIN RESULTS: Bioassays revealed significantly decreased release of all studied interleukins (interleukins-1, -2, -3, and -6) by peritoneal and splenic macrophages as well as significantly decreased splenocyte proliferative capacity after shock in vehicle-treated mice. Naloxone administration after hemorrhage resulted in either similar or even more decreased levels of interleukin release compared with vehicle-treated hemorrhaged mice. Significantly increased plasma corticosterone concentrations were observed in vehicle-treated animals compared with control animals. Naloxone administration did not have any significant effects on corticosterone plasma concentrations after hemorrhage. CONCLUSIONS: These findings indicate the importance of the endogenous opioid system for the maintenance of immunity in adverse circulatory conditions, i.e., hemorrhage. Although additional studies involving different doses and/or times of naloxone administration may provide different results, the present findings raise the concern that naloxone administration in the traumatized host may have deleterious effects because it decreases peritoneal macrophage and splenic immune functions.

Animals↗

PubMed2000

Incidence of septic complications and multiple organ failure in severely injured patients is sex specific.

BACKGROUND: Sexual hormones are potent regulators of various immune functions. Although androgens are immunosuppressive, estrogens protect against septic challenges in animal models. This study correlates sexual dimorphism with the incidence of posttraumatic complications in severely injured patients. METHODS: From January of 1991 to February of 1996, 1,276 consecutive injured patients (Injury Severity Score [ISS] > or = 9 points) were studied. Males (n = 911) did not differ from females (n = 365) with regard to severity of injury (ISS) and injury pattern. RESULTS: The incidence of posttraumatic sepsis (30.7%) and multiple organ dysfunction syndrome (29.6%) was significantly increased in severely injured males with ISS > or = 25 points in comparison to the equivalent group of females (sepsis, 17.0%; multiple organ dysfunction syndrome, 16.0%). No difference was found in patients with ISS < 25 points. Moreover, plasma levels of procalcitonin and interleukin-6 were elevated (p < 0.05) in severely injured males compared with females. CONCLUSION: Sex influences posttraumatic morbidity in severely injured patients and supports the concept that females are immunologically better positioned toward a septic challenge.

Adult↗

PubMed1999

Minimal invasive treatment of proximal femur fractures with the long gamma nail: indication, technique, results.

BACKGROUND: The surgical treatment of complex unstable proximal femur fractures from the trochanteric region to the middle shaft area is difficult and often highly invasive, especially in older patients with osteoporotic bones. METHODS: In 1993, we began to treat all unstable proximal femur fractures from the trochanteric region to the middle third of the shaft with the long gamma nail (LGN) and allowed the patients immediate full weightbearing after surgery. Perioperative, postoperative, and follow-up data were analyzed. RESULTS: During a 3-year period, we treated 37 patients with unstable proximal femur fractures with the LGN. Five of the patients had sustained pathological fractures, and four patients had sustained multiple trauma. The 37 operations were performed by 22 different surgeons with varying degrees of experience. The LGN implantations through maximal 40-mm skin incisions were performed in a mean skin-to-skin operation time of 125 minutes (range, 65-200 minutes) without any further complications. Thirty-one of the 37 patients were allowed immediate full weightbearing after the second postoperative day. The six patients who were not allowed full weightbearing were the ones who had multiple trauma (4) and those who were unable to walk before surgery (2). Three postoperative complications were as follows: one deep infection 4 months after surgery, one superficial infection 3 weeks after surgery, and one deep vein thrombosis 2 weeks after discharge. All three complications occurred in the group of patients who had sustained only one trauma. All traumatic fractures (n = 32) healed without any bone grafting, which means a union rate of 100%. Although immediate full weightbearing was allowed, there were no implant dislocations, implant failures, or other problems. The 30-day mortality was 0%. The follow-up examinations after a mean time of 6 months were very satisfying. All traumatic fractures were healed. The patients had symmetrical functional findings to the opposite side or before surgery, respectively, except for two patients with a leg shortening of 2 cm, two patients with an external malrotation of 10 degrees, and one patient with a hip extension deficit of 10 degrees after a pathological fracture. CONCLUSION: The LGN is, after appropriate introduction and training, a safe and easy implant for the treatment of complex proximal femur fractures from the trochanteric region to the middle shaft area. The minimal invasive technique with low risks and minimal complications and the possibility of immediate full weightbearing sets a new standard, especially for older patients with osteoporotic bones.

Adolescent↗

PubMed1998

Metoclopramide: a novel and safe immunomodulating agent for restoring the depressed macrophage immune function after hemorrhage.

BACKGROUND AND OBJECTIVE: Recent studies have shown that administration of the anterior pituitary hormone, prolactin, after hemorrhage restored the depressed immune responses that are observed under those conditions. Because metoclopramide (MCP) is known to increase prolactin secretion and ultimately plasma prolactin levels, we attempted to determine whether administration of metoclopramide after hemorrhage produces any beneficial effects on the depressed splenocyte and peritoneal macrophage immune function after severe hemorrhage. DESIGN, MATERIALS AND METHODS: Mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 minutes, then adequately resuscitated and segregated into two groups. One group received saline vehicle; animals in the other group were treated with metoclopramide (100 microg/100 g body weight, subcutaneously) before resuscitation. Two hours after saline or MCP injection, the animals were killed and macrophage as well as splenocyte cultures established. Plasma corticosterone levels were also measured. RESULTS: The proliferative capacity of the splenocytes as well as their ability to release interleukin (IL)-2 and IL-3 in response to mitogen was markedly improved in animals that had hemorrhaged and that were treated with MCP compared with saline-injected mice. Moreover, the depressed splenic and peritoneal macrophage IL-1 and IL-6 release after hemorrhage was restored with MCP treatment. Furthermore, treatment with MCP prevented the increase in blood corticosterone levels seen after severe hemorrhage. CONCLUSION: These results support the concept that the immunosuppression after hemorrhage may be mediated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, MCP may be a useful adjuvant in the treatment of the trauma-hemorrhagic shock-induced immunosuppression.

Animals↗

PubMed1997

Effects of prolactin and metoclopramide on macrophage cytokine gene expression in late sepsis.

Previous studies indicate a profound suppression of tumour necrosis factor alpha (TNF-gamma), IL-1 beta and IL-6 release capacity by peritoneal macrophage (PM phi), splenic macrophage (SM phi) and Kupffer cells (KC) during late sepsis. Such a loss of functional capacity may reduce the animal's ability to ward off infection. Prolactin is known to enhance monocyte, T- and B-lymphocyte immune responses under normal conditions and has beneficial effects on cell-mediated immunity after haemorrhage. In the respect, the dopamine antagonist, metoclopramide, has been reported to increase circulating prolactin levels. Nonetheless, it remains unknown whether prolactin or metoclopramide have any salutary effect on macrophage (M phi) cytokine gene expression following sepsis. To study this, male C3H/HeN mice were subjected to sepsis and immediately thereafter were treated with prolactin (100 micrograms/25 g body weight, s.c.), metoclopramide (100 micrograms/100 g BW, s.c.) or given saline. PM phi, SM phi and KC (only SM phi and KC in metoclopramide-treated animals) were isolated at 24 h after sepsis. The monolayers were stimulated with or without LPS 10 micrograms/ml for 1 h in vitro. Total RNA was extracted and mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). A significant depression of constitutive and inducible mRNA levels of IL-1 beta, IL-6 and TNF-alpha in all three M phi populations were observed, when compared with shams (with exception of KC IL-6 mRNA in unstimulated cells). Prolactin as well as metoclopramide treatment after the onset of sepsis caused significant elevation of constitutive and inducible cytokine gene expression in all macrophages examined. Thus, prolactin and metoclopramide enhance the depressed M phi gene expression and may be useful in improving cell-mediated immunity during sepsis.

Animals↗

PubMed1997

[Testing bone implants in cell lines and human osteoblasts].

Two different types of cell-line and fresh human osteoblasts, cultured from cancellous bone grafts from the iliac crest, were used for the study. Three different biomaterials were compared regarding biocompatibility: titanium, steel and hydroxyapatite. The cells were fibroblast cell line (3T3), "osteoblast-like" cell line (MC3T3-E1), and fresh human osteoblasts (HOB) which we cultured in our laboratory. 5 x 10(4) cells of each type were seeded on the three different bone implants. All experiments were performed in triplicate. Cell proliferation and alkaline phosphatase activity were determined 24 and 72 h after the cells were plated on the biomaterials. Human osteoblast growth was better on titanium than on steel and hydroxyapatite. The most remarkable observation was the continuously decreasing alkaline phosphatase activity (ALP) of "osteoblast-like" cells (MC3T3-E1) and human osteoblasts (HOB) on hydroxyapatite. In conclusion, our in vitro observations suggest that the best cell/material interactions were with human osteoblasts (HOB) and titanium.

Bone Plates↗

PubMed1997

Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males.

OBJECTIVES: To determine: a) whether the cell-mediated immune response during sepsis differs in females vs. males; and b) whether the survival rate in females is different than in males after a septic insult. DESIGN: A prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female proestrus C3H/HeN mice. INTERVENTIONS: After anesthesia, male and proestrus female mice underwent cecal ligation puncture to induce sepsis. The mice were killed at 24 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: Splenocyte proliferation, as well as splenocyte interleukin (IL)-2 and IL-3 release, was determined by bioassay. In additional studies, survival rate after septic challenge was measured over 10 days. Splenocyte proliferative capacity and splenocyte IL-2 and IL-3 release were markedly decreased in male, but not in female, septic mice. Furthermore, the survival rate of septic female proestrus mice was significantly higher than in comparable male mice. CONCLUSIONS: These results support the concept that the immune response of females differs from males, and that females are immunologically better positioned to meet the challenge of sepsis.

Adolescent↗

PubMed1996

Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis.

Although prolactin is reported to counteract the immunosuppressive effects of glucocorticoids, cyclosporine, and morphine, it remains unknown whether prolactin 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 divided into two groups. One group received saline vehicle, while the other group received prolactin (100 micro g/25 g body weight, s.c.) immediately before resuscitation. Two hours thereafter, peritoneal (pMphi) and splenic macrophages (sMphi) were harvested and assessed not only for their ability to release IL-1 and IL-6, but also for cytokine gene expression using semiquantitative reverse transcription and PCR. In an additional group, mice were subjected to sepsis by cecal ligation and puncture 3 days after hemorrhage. Hemorrhage markedly decreased the ability of pMphi and sMphi to release IL-1 and IL-6. This was, however, associated with increased mRNA expression for IL-1beta and IL-6 and increased serum corticosterone levels. Following prolactin treatment of hemorrhaged mice, IL-1beta and IL-6 mRNA levels as well as cytokine release capacity and blood corticosterone levels were comparable to the values in sham animals. Prolactin also improved the survival of animals subjected to sepsis after hemorrhage. Thus, the immunosuppression following hemorrhage appears to be mediated and modulated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, prolactin represents a novel immunomodulating hormone for the treatment of immunodepression encountered after hemorrhagic shock and for decreasing the mortality from subsequent sepsis under those conditions.

Animals↗

PubMed1996

Increased melatonin levels after hemorrhagic shock in male and female C3H/HeN mice.

Although hemorrhagic shock leads to significant alterations of several hormones, e.g. ACTH, corticosterone and beta-endorphin, it is not known whether plasma melatonin levels are affected under this condition and if so, whether the effects are comparable in males and females. Using a radioimmunoassay, it was found that plasma melatonin levels were significantly increased in male and proestrus female C3H/HeN mice immediately after hemorrhagic shock. However, in male mice, by two hours after hemorrhage and resuscitation, plasma melatonin returned to levels comparable to those seen in control and sham-operated animals. Proestrus female mice, on the other hand, showed significantly increased plasma melatonin levels at two hours after surgery when compared to unoperated control animals. Although the significance and biological role of the transient increased plasma melatonin levels after hemorrhagic shock remain to be determined, it appears that the pineal gland and/or an extrapineal source of melatonin, of both male and proestrus female mice responds to severe hypotension by increased release of melatonin.

Animals↗

PubMed1996

Immune function is more compromised after closed bone fracture and hemorrhagic shock than hemorrhage alone.

OBJECTIVE: To determine whether closed bone fracture in conjunction with hemorrhagic shock compromises immune functions more severely than hemorrhagic shock alone. DESIGN: In a randomized, controlled trial, closed bone fracture of the right lower leg and/or hemorrhagic shock (mean +/- SEM arterial blood pressure, 35 +/- 5 mm Hg for 90 minutes) were induced in male C3H/HeN mice (weight, 25 g). Animals subjected to hemorrhage were resuscitated with the shed blood and lactated Ringer solution. At 72 hours after the experiment, all animals were killed to obtain whole blood, splenocytes, and splenic and peritoneal macrophages. Macrophage interleukin-1 and splenocyte interleukin-2 and interleukin-3 release were determined by bioassay, and splenocyte proliferation was measured by tritiated thymidine incorporation. RESULTS: Closed bone fracture alone did not affect immune functions 72 hours after the trauma. Hemorrhagic shock, however, induced a significant depression of splenocyte and macrophage functions. Bone fracture followed by hemorrhagic shock further depressed splenocyte proliferation and splenocyte interleukin-2 and interleukin-3 release as well as interleukin-1 release. CONCLUSION: Since bone injury coupled with hemorrhagic shock produces more severe depression of immune functions than hemorrhage alone, bone injury appears to play a contributory role in further depressing immune functions in trauma patients who experience major blood loss.

Animals↗

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

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↗

PubMed1995

Cytokine gene expression in splenic macrophages and Kupffer cells following haemorrhage.

TNF-alpha, IL-1, IL-6 and TGF-beta are important macrophage-derived mediators which play the pleiotropic role in inflammatory, metabolic, hematopoietic and immunologic processes. Studies have shown that haemorrhagic shock without significant tissue trauma induces profound immunosuppression which is associated with elevated plasma levels of TNF-alpha IL-1, IL-6 as well as TGF-beta. Furthermore, Kupffer cells but not the splenic M phi isolated from post-haemorrhaged animals showed an increased capacity to release inflammatory cytokines in response to LPS stimulation in vitro. However, it remains unknown whether the innate (i.e. in the absence of LPS stimulation) cytokine genes expression in Kupffer cells and splenic M phi is affected by haemorrhage. To determine this, C3H/HeN male mice were bled to and maintained at a mean arterial blood pressure of 35 mmHg for 60 min, and then adequately resuscitated. Splenic macrophages and Kupffer cells were isolated at 1 h after haemorrhage. Total RNA was extracted and cytokine mRNA was detected by semi-quantitative reverse transcription and polymerase chain reaction (RT-PCR). The results demonstrate that haemorrhage significantly elevated the mRNA accumulation of TNF-alpha, IL-1 beta, TGF-beta while IL-6 gene expression in Kupffer cells and splenic M phi was only slightly increased. Since Kupffer cells but not the splenic M phi showed increased cytokine release, it could be concluded that the differential regulation of cytokine release by these two macrophage populations following haemorrhage may be due to the divergence of the cytokine at the translational level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗