Prospective observational study of antiphospholipid antibodies in acute lung injury and acute respiratory distress syndrome: comparison with catastrophic antiphospholipid syndrome.

Detection of antiphospholipid (aPL) antibodies in bronchoalveolar lavage fluid (BALF) of patient with acute respiratory distress syndrome (ARDS) suggests involvement of autoimmune mechanisms in the pathogenesis of ARDS. We investigated whether aPL antibodies could be detected in the serum as well as BALF of patients with acute lung injury (ALI) and ARDS. IgG anticardiolipin, IgG anti-beta2-glycoprotein I, IgG antiphosphatidic acid and IgG antiphosphatidylserine antibodies were detected by ELISA in low titers within the normal range in the BALF and serum of nine patients with ALI and 17 patients with ARDS. However, one out of 27 patients investigated had high levels of aPL antibodies in both BALF and serum. This patient suffered from severe ARDS due to sepsis. The high aPL antibody levels in serum possibly triggered by sepsis were associated with high aPL antibody levels in BALF, which can be explained by high capillary-alveolar permeability. Computed tomography scan revealed widespread infarctions in brain, spleen and kidneys, and pulmonary thromboembolism, suggesting the diagnosis of catastrophic antiphospholipid syndrome.

Are leukocytes in salvaged washed autologous blood harmful for the recipient? The results of a pilot study.

To explore whether polymorphonuclear leukocytes (PMNL) are activated to the priming threshold through intraoperative blood salvage, and are thus able to induce endothelial damage, we investigated chemotactic response (n = 20) and respiratory burst (RB; n = 20) of PMNL without (basal respiratory burst, bPMNL-RB) and after in vitro stimulation with formyl-Met-Leu-Phe (fMLP-RB) and phorbol myristate acetate (PMA-RB). Blood was processed with a continuous autotransfusion device (CATS). Heparin (Heparin group) and sodium citrate (Citrate group) were used alternately as an anticoagulant for each half of the chemotaxis and RB studies. Comparison of measurements from the processed autologous erythrocyte concentrates (paEC) to pre- and intraoperative arterial blood samples showed no statistically significant difference for any test of PMNL functional responses in an orthopedic patient population. Analysis of intraindividual changes demonstrated a significantly increased bPMNL-RB (both groups, P = 0.0032; Heparin group, P = 0.0098), fMLP-RB (both groups, P = 0.0484; Citrate group, P = 0.0371), and PMA-RB (Citrate group, P = 0.002) in the paEC compared with intraoperative arterial samples, whereas the chemotactic response did not change. Nevertheless, median values of all RB measurements in the paEC were within the range of pre- and intraoperative values, indicating that PMNLs contained in the paEC are neither impaired nor activated to the priming threshold. The results confirm the clinical experience that intraoperative blood salvage is safe to use during major orthopedic surgery and questions the beneficial effect of special leukocyte-removing filters.

Plasma levels of procalcitonin and interleukin-6 in acute myocardial infarction.

Estimation of cardiac morbidity in patients after major surgery is a difficult problem. In addition, infectious complications seriously decrease potential beneficial outcome after cardiovascular surgery. The present study assessed the use of a newer marker of the inflammatory response, procalcitonin, in the field of myocardial infarction, in conjunction with measurements of interleukin-6. Forty-four consecutive cases with acute myocardial infarction were included in the study 4+/-1.3 h after the onset of symptoms. Plasma levels of procalcitonin and interleukin-6 were obtained at admission, and after 3, 6, 12, 18, 24 and 48 h, using commercially available test kits. The range of levels of interleukin-6 and procalcitonin was about normal at admission. Interleukin-6 levels increased significantly following myocardial infarction, whereas procalcitonin were essentially unchanged, i.e. remained close to the normal level threshold of 0.5 ng/ml; only minor variability occurred with a mean peak level of procalcitonin of 1+/-0.4 ng/ml. Data demonstrate that, in contrast to the acute phase reactant interleukin-6, plasma levels procalcitonin are not significantly elevated during uncomplicated acute myocardial infarction. This observation may support the role of procalcitonin measurements in the differential diagnosis of infectious and cardiovascular complications after major surgery.

Recombinant granulocyte colony-stimulating factor (G-CSF) in infectious diseases: still a debate.

Granulocyte colony-stimulating factor (G-CSF), a central mediator of the endogenous response to infection and inflammation, is approved for use in the prevention of infection-related complications in patients with nonmyeloid malignancies during antineoplastic therapy associated with high risk of severe neutropenia. Administration of granulocyte colony-stimulating factor results in improvement of host defence paired with anti-inflammatory effects. There is evidence from animal and clinical studies that administration of granulocyte colony-stimulating factor may also be beneficial in non-neutropenic infections. This review focuses mainly on the results of different animal and clinical studies of granulocyte colony stimulating factor used in the treatment of severe infections and sepsis.

In vitro modulation of inducible nitric oxide synthase gene expression and nitric oxide synthesis by procalcitonin.

OBJECTIVE: Serum procalcitonin (PCT) concentration was recently introduced as valuable diagnostic marker for systemic bacterial infection and sepsis. At present, the cellular sources and biological properties of PCT are unclear. During sepsis and septic shock, inducible nitric oxide synthase (iNOS) gene expression is stimulated followed by the release of large amounts of nitric oxide (NO). We investigated the possible association between PCT and iNOS gene expression in an in vitro cell culture model. DESIGN: Prospective, controlled in vitro cell culture study. SETTING: University research laboratories. INTERVENTIONS: Confluent rat vascular smooth muscle cells (VSMC) were incubated for 24 hrs and 48 hrs with PCT (1 ng/mL, 10 ng/mL, 100 ng/mL, 1,000 ng/mL, 5,000 ng/mL) alone or with the combination of tumor necrosis factor-alpha (TNF-alpha, 500 U/mL) plus interferon-gamma (IFN-gamma, 100 U/mL). iNOS gene expression was measured by qualitative as well as quantitative polymerase chain reaction analysis, NO release was estimated by the modified Griess method. MEASUREMENTS AND MAIN RESULTS: PCT in increasing concentrations had no effect on iNOS gene expression and nitrite/nitrate release for 24 hrs and 48 hrs, respectively. However, PCT ameliorated TNF-alpha/IFN-gamma-induced iNOS gene expression in a dose-dependent manner (maximal inhibition at PCT 100 ng/mL by -66% for 24 hrs and -80% for 48 hrs). This was accompanied by a significantly reduced release of nitrite/nitrate into the cell culture supernatant (maximal reduction at PCT 100 ng/mL by -56% and -45% for 24 hrs and 48 hrs, respectively). CONCLUSIONS: We conclude that recombinant PCT inhibits the iNOS-inducing effects of the proinflammatory cytokines TNF-alpha/ IFN-gamma in a dose-dependent manner. This might be a counter-regulatory mechanism directed against the large production of NO and the concomitant systemic hypotension in severe sepsis and septic shock.

Low platelet count and elevated serum thrombopoietin after severe trauma.

Platelet count is regularly low in patients after multiple trauma, mainly due to blood loss and dilution. Thrombopoietin (TPO) is the main regulator of the circulating platelet mass. Under several clinical conditions an inverse correlation between TPO and the circulating platelet mass was reported. Since platelets bind and internalize TPO, a platelet-dependent regulation of TPO was suggested. Thus, acute blood loss should be accompanied by elevated TPO. We measured serum TPO, platelets, interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in 17 multiple traumatized victims. Blood was collected within 12 h after trauma as well as in the morning of days 2, 4, 6 and 9 after admission at the intensive care unit. Platelet count was low at admission and remained low until day 4. Thereafter platelets increased until day 9. TPO nearly doubled within the first 2 d, reaching its maximum on day 6. IL-6 was initially very high and steadily decreased until day 9. VEGF increased 3-fold during the 9 d. Statistically significant correlations of TPO were found with platelets and IL-6, but not with VEGF. In multiple traumatized patients low platelet count is followed by a rapid increase in serum TPO. This fits into the concept of a feedback regulation between circulating TPO and platelet mass.

Acute respiratory failure associated with catastrophic antiphospholipid syndrome.

We present a case of multiple organ dysfunction syndrome with acute respiratory failure due to alveolar haemorrhage associated with antiphospholipid antibodies in a 42-year-old woman with a medical history of antinuclear antibody-negative systemic lupus erythematosus and antiphospholipid syndrome. Severe respiratory failure, circulatory shock and acute renal failure necessitated artificial ventilation, inotropic and vasopressor therapy, and continuous venovenous haemofiltration. A tentative diagnosis of haemorrhagic lupus pneumonitis or pulmonary manifestation of antiphospholipid syndrome was made. Lupus anticoagulant, IgG anticardiolipin and anti-beta2-glycoprotein I antibodies were positive. High-dose glucocorticoid, anticoagulation with heparin, plasmapheresis and cyclophosphamide improved her clinical condition. Despite this, the patient died several days later of spontaneous intracranial haemorrhage. This case illustrates the uncommon manifestation of acute respiratory failure associated with antiphospholipid syndrome.

Induction of normal human eosinophil migration in vitro by substance P.

To investigate the role of tachykinins in allergic inflammation, the effect of substance P (SP) on normal human eosinophil migration was examined in Boyden chamber type assays. SP stimulated eosinophil migration in vitro with an EC50 of about 1-10 pM and maximal effects were seen at 100 pM. A carboxy-terminal fragment of SP possessed appreciable activity whereas an amino-terminal fragment was inactive. Data represented in this paper and previous studies suggest that eosinophils are attracted by SP and activated to enhanced mediator release and cytotoxic activity.