Effect of blood transfusion on antigen presentation function and on interleukin 2 generation.

To study the effect of blood transfusion (BT) on cell-mediated immunity, we examined the antigen presentation function of peritoneal macrophages and interleukin 2 (IL-2) generation by splenocytes. C3H/HEJ mice were transfused with 0.2 mL of fresh allogeneic blood obtained from C57BL/6 mice; they were killed on days 1, 3, and 7 after BT. A second group of C3H/HEJ mice was transfused with 0.2 mL/d of the same allogeneic blood on three successive days; they were killed on day 7 following the last BT. The antigen presentation function of peritoneal macrophages was measured by utilizing a D10.G4.1 T-helper cell clone; IL-2 activity in supernatants of concanavalin A-stimulated splenocytes was tested by utilizing an IL-2-dependent HT-2 cell line. The results indicate that although antigen presentation function remains unaffected after single and multiple BTs, the ability of splenocytes to generate IL-2 decreases significantly even after a single BT. Thus, the increased susceptibility to infection and the additional immune perturbations in malignant neoplasms following BT may be due in part to decreased IL-2 generation.

Does endotoxin tolerance prevent the release of inflammatory monokines (interleukin 1, interleukin 6, or tumor necrosis factor) during sepsis?

Mice were subjected to sepsis by cecal ligation and puncture to determine whether macrophages from endotoxin-tolerant C3H/HeJ mice are also activated systemically to release inflammatory monokines associated with septic mortality. Blood levels of both tumor necrosis factor and interleukin 6 were significantly elevated during the first 1 to 4 hours of sepsis as compared with sham controls. Peritoneal macrophages from septic mice exhibited a marked spontaneous release of interleukin 1, interleukin 6, and tumor necrosis factor at 1 hour. However, the addition of endotoxin to macrophage cultures taken from septic mice had no further stimulatory effect. Sham controls alternatively showed no significant innate monokine release, but their macrophages did release increased monokine numbers in response to endotoxin. These results indicate that the spontaneous macrophage release of these monokines is comparable with that previously observed in endotoxin-sensitive mice, suggesting a common mechanism by which macrophages are primed by traumatic injury by an agent other than endotoxin to release monokines during sepsis. Thus, the administration of agents that decrease or prevent the deleterious effects of systemic inflammatory mediators during sepsis could be useful adjuvants in those clinical situations where the bacterial origin is unknown.

Laparoscopic is not better than open appendectomy.

Laparoscopic appendectomy is increasingly being used by general surgeons. The advantages of the procedure over open appendectomy are not as obvious as the advantages of laparoscopic cholecystectomy over open cholecystectomy. This study was a retrospective review of nonrandomized patients of two attending surgeons over the time period 4/11/91 to 2/15/93. Parameters examined included patient age, gender, operating room time, hospital cost, hospital stay, negative appendectomy rate, and wound infection rate. Results showed that there was no difference in the patient age. Gender was significantly different, with the laparoscopic group containing 68% females, whereas the open group contained only 39% (P < 0.01). Operating room time was significantly longer for the laparoscopic group by approximately 18 minutes (P < 0.05). Hospital cost was $1400.00 more expensive for the laparoscopic group (P < 0.05). Hospital stay and wound infection rates were not significantly different. The negative appendectomy rate was 37% for the laparoscopic group and 12% for the open group (P < 0.05). We conclude that laparoscopic is not superior to open appendectomy.

Is laparoscopic better than open appendectomy?

Laparoscopic appendectomy is becoming increasingly popular as surgeons strive to manage surgical problems via minimally invasive techniques. We reviewed our early experience in 38 patients with laparoscopic appendectomy and compared it to open appendectomies done during the same time period. We found no difference in hospital costs, stay, or wound infection rate. There was a significant difference in OR time: the laparoscopic approach took longer. We conclude that this new approach is not clearly superior to open appendectomy despite theoretical advantages. Newer instruments and further studies are needed.

Polymicrobial sepsis selectively activates peritoneal but not alveolar macrophages to release inflammatory mediators (interleukins-1 and -6 and tumor necrosis factor).

While a number of clinical studies indicate that elevated serum cytokine [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF)] levels are associated with enhanced mortality in sepsis, the time course and the role that different macrophage (M phi) populations play in releasing these cytokines remain to be determined. To study this, polymicrobial sepsis was induced in C3H/HeN mice by cecal ligation and puncture (CLP). The animals were then sacrificed at 1, 4, or 24 hr post-CLP. Blood was taken for serum cytokine level determination. Macrophages, of either peritoneal (PM phi) or alveolar (AM phi) origin, were harvested by lavage, and their innate vs. inducible cytokine productive capacities were assessed by incubation with or without endotoxin (lipopolysaccharide; LPS). Serum levels of TNF were significantly enhanced 1 hr post-CLP (CLP = 3.8 +/- 2.4* vs. sham = 0.4 +/- 0.9 U/ml; P less than 0.05 by t test). However, not until 4 hr post-CLP were marked increases in IL-6 observed (CLP = 318.0 +/- 209.0* vs. sham = 1.1 +/- 0.5 U/ml), which remained elevated through 24 hr post-CLP (CLP = 11.3 +/- 15.0* vs. sham = 0.03 +/- 0.02 U/ml). Cytokine release (IL-1, IL-6, TNF) from PM phi (without the addition of LPS) was detectable only in cells harvested 1 h following CLP. Alveolar M phi from septic mice showed little in vivo activation. Septic PM phi IL-1 and IL-6 production was markedly depressed at all time points with LPS stimulation, but TNF release remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

A model of pulmonary atelectasis in rats: activation of alveolar macrophage and cytokine release.

Although atelectasis frequently occurs after surgery and trauma, and such patients have elevated body temperatures, the mechanism of temperature elevation secondary to atelectasis is unknown. Moreover, a small animal model has not been available to study the pathophysiology of pulmonary atelectasis. The purpose of this study, therefore, was to develop a model of pulmonary atelectasis in rats. Because interleukin-1 (IL-1) and tumor necrosis factor (TNF), both potent pyrogens, are produced by macrophages during infection and inflammation, our aim was also to determine whether alveolar macrophages produce IL-1 or TNF in response to atelectasis. Whole-lung atelectasis was produced in rats by ligating the left main stem bronchus while maintaining ventilation of the right lung. After a 1-h period of atelectasis, alveolar macrophages were harvested from the right and left lungs and incubated for 24 h, and the supernatants were assayed for IL-1 and TNF. Both IL-1 and TNF levels of macrophage cultures from the atelectatic lung were significantly increased compared with the control lung. These results suggest that increased IL-1 or TNF production by alveolar macrophages may be responsible for fever caused by atelectasis.

Pentoxifylline attenuates oxygen-induced lung injury.

Patients requiring mechanical ventilation can develop severe pulmonary injury. Although pentoxifylline (PTX) is known to attenuate endotoxin and tumor necrosis factor (TNF)-induced lung injury, as well as decrease interleukin-6 (IL-6) levels following hemorrhage and resuscitation, it remains unknown if this agent has any beneficial effects against O2-induced lung injury. The aim of this study, therefore, was to determine if PTX attenuates pulmonary oxygen toxicity. To investigate this, male Sprague-Dawley rats were injected subcutaneously with 1 ml saline or 1 ml PTX (50 mg/kg) and immediately exposed to either 21% O2 or > or = 95% O2 for 52 hr. The animals were then reweighed and euthanized. Pleural fluid was collected, blood samples were obtained, and lung lavage was performed. Lactate dehydrogenase (LDH) activity, protein content, and IL-6 concentrations were determined in the lavage fluid and serum. The supernatant LDH activity, protein content, pleural fluid accumulation, and IL-6 concentration were significantly decreased (P < 0.05) in those animals pretreated with PTX prior to exposure to hyperoxia compared to those animals exposed to hyperoxia and not treated. Furthermore, the hematocrit and serum IL-6 concentration were also decreased in the treated group and not significantly different from the controls. Thus, PTX appears to attenuate O2-induced lung injury and may play a role in protecting those patients at risk for developing pulmonary oxygen toxicity.