Bronchoalveolar lavage and plasma Antithrombin and cytokines in inhalation and burn injury: a pilot study.

Systemic inflammatory response syndrome (SIRS) is initiated during the acute phase of thermal injury. The objective was to determine the SIRS impact on cytokine and Antithrombin (AT) levels in smoke inhalation and burn injury. This observational pilot study compared plasma and bronchoalveolar lavage fluid (BAL) cytokine and AT levels in the first six days post smoke inhalation and burn injury. Twenty-five patients, 14 with inhalation + burn injury > 10% total body surface area (TBSA) and 11 with inhalation injury and ≤ 10% TBSA participated. Human Th1/Th2 cytometric bead array kit from BD Biosciences Pharmingen determined cytokine levels; AT levels with Sigma Diagnostics and spectrophotometry. Results indicated no significant age difference between the two groups (42.1 ± 7.2) versus 49.6 ± 6.4 years. On admission, the inhalation group had 5.4 ± 3.9% TBSA compared to 35.0 ± 22.2% TBSA in the inhalation + burn group, P < 0.001. Comparing groups, AT plasma levels were significantly decreased (P = 0.025) and IL-2 levels significantly increased (P = 0.025) in the inhalation + burn group compared to the inhalation group; there was no significant difference in BAL AT or cytokine levels. Combined group plasma AT levels (65.41 ± 4.44%) were significantly increased compared to BAL AT levels (1.06 ± 0.71%), P < 0.001. In contrast, BAL TNF-α levels (35.61 ± 16.01 pg/ml) were significantly increased in relation to the plasma levels (4.68 ± 1.27 pg/ml), P = 0.02. On days 1-2, AT plasma levels were significantly decreased in the inhalation + burn group (41.01 ± 5.24%) compared to the inhalation group (81.02 ± 10.99%), P = 0.002. IL-6 plasma levels were higher in the inhalation + burn group compared to the inhalation group on admission, but both levels decreased by days 3-6. IL-6 BAL levels were elevated in both groups on days 1-2 and decreased by days 3-6. In the first six days of resuscitation, all plasma cytokines were increased in the two groups compared to controls. AT plasma and BAL levels were significantly reduced in both groups, contributing to the coagulopathy. Increased BAL TNF-α and IL-6 levels may have contributed to the pulmonary perturbations during the initial SIRS response in both groups.

TAKEDA-143242 increased survival via reduced cytokines in porcine peritonitis.

TAKEDA-143242 (TAK-242) is a small molecule shown to inhibit lipopolysaccharide-induced intracellular signaling and inflammation. In vitro studies demonstrated that TAK-242 can prevent release of TNF-α, IL-1ß, and IL-6 from activated macrophages of several species, including pigs. This study tested the hypothesis that TAK-242 would protect pigs from lethal gram-negative peritonitis via an anti-cytokine mechanism. A validated model of porcine gram-negative peritonitis, which employs chronically inplantated cardiac transducers and aortic and pulmonary artery catheters, was used. Pigs were pretreated with TAK-242 or its vehicle via a blinding procedure prior to intraperitoneal implantation of an LD(90) dose of E. coli 0111:B4 in a fibrin clot. Ten pigs were treated with TAK-242 and nine with its vehicle. All ten TAK-242 treated pigs survived, while three of the nine vehicle treated pigs survived (P = 0.01 χ(2) test). Pulmonary artery pressure increased markedly in vehicle pigs, and this elevation was significantly (two-way ANOVA) obviated in TAK-242 treated group. Circulating levels of cytokines in vehicle treated pigs showed increased expression (3930 ± 1770 at 1 h, 1007 ± 400 TNF-α at 2 h; 719 ± 308 of IL-1ß at 2-6 h; 33000 ± 1000 of IL-6 at 2-4 h [pg/mL, mean ± SEM]). Peak circulating levels of these cytokines were significantly reduced by pretreatment with TAK-242 (<25 pg/mL TNF-α ; <100 pg/mL IL-1ß; 0-1700 pg/mL IL-6, peak values). This study found that pretreatment with TAK-242 yielded significantly positive survival benefit in a lethal sepsis model that was associated with improved cardiovascular status and suppressed cytokine release.

Elevated cytokine levels in peritoneal fluid from burned patients with intra-abdominal hypertension and abdominal compartment syndrome.

BACKGROUND: Burn patients with intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) undergo vigorous resuscitation and accumulate peritoneal fluid (PF) that is a plasma ultra-filtrate. This study compared antithrombin (AT) and cytokine levels in burn patient plasma and peritoneal fluid (PF). METHODS: Twenty-nine patients were studied: 22 developed IAH and 9 progressed to ACS. Burn + inhalation injury was present in 22 patients; 5 had burn only and 2 had inhalation only. Sixteen patients died: of these, 9 survived less than 48 h due to the severity of their injuries. Flow cytometry utilized the Cytometric Bead Array kit for Human Th1/Th2 cytokines. AT levels were determined by the Accucolor method spectrophotometrically. RESULTS: All cytokine levels were significantly elevated in burn plasma and PF compared to normal plasma, p < 0.001. AT plasma levels were decreased compared to normal. AT and cytokines were present in peritoneal fluid of burn patients with IAH and ACS. Patients who died had decreased plasma levels of AT and increased IFN-gamma, IL-10, IL-6, IL-4, IL-2 peritoneal fluid levels compared to survivors. CONCLUSIONS: Peritoneal fluid may be a reservoir for cytokines during initial resuscitation and contributes to homeostatic perturbations in burn patients.

Metal fume fever presenting as aseptic meningitis with pericarditis, pleuritis and pneumonitis.

BACKGROUND: Metal fume fever (MFF) is a well-known complication of zinc oxide fume inhalation. Prompt recognition of this condition is essential for the proper medical management of this self-limited disease. AIM: To present a unique and unusual case of MFF. RESULTS: Our patient is a 25-year-old male welder who had MFF and presented with aseptic meningitis with pericarditis, pleuritis and pneumonitis. To our knowledge, this is the first case of MMF presenting with these signs and symptoms. CONCLUSIONS: MFF can present with a systemic inflammatory response causing a multi-organ serositis. Our case highlights the utmost importance of obtaining an occupational history on all our patients, even if they are critically ill.

Circulating endothelial cell levels correlate with proinflammatory cytokine increase in the acute phase of thermal injury.

Circulating endothelial cells (CECs) are increased in sickle cell disease, myocardial infarction, and acute lung injury. The purpose of this study was to determine whether CECs are a prognosticating marker for the development of pneumonia in burn patients with/without inhalation injury in addition to their relationship to proinflammatory cytokines. There were 24 patients: 6 with inhalation injury, 5 with burn only,and 13 with burn plus inhalation injury. CECs were measured by anchored cytometry (Clarient ChromaVision, San Juan Capistrano, CA). In addition, plasma levels of tumor necrosis factor-alpha, interferon-gamma, and interleukins (IL)-10, IL-6, IL-4, and IL-2 were compared with CEC levels. Patients with inhalation injury had a significant (P < .001) paucity of CECs compared with the thermally injured with inhalation. There was a statistically significant increase in inteferon-gamma, tumor necrosis factor-alpha, and IL-6, IL-4, and IL-2 compared with control patients (P < .01), with a concomitant increase in the number of CECs. The numbers of CEC levels did not prognosticate which patients would develop pneumonia. Burn patients with/without inhalation injury had concurrent increase in CECs and proinflammatory cytokines during the acute phase of injury.