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Casey M Calkins

Publications and source records attributed to Casey M Calkins.

24 records · Page 2Linked to original sources
PubMed2002

Altered neutrophil function in the neonate protects against sepsis-induced lung injury.

BACKGROUND/PURPOSE: Neutrophils (PMNs) are well known effectors of lung injury after sepsis. The accumulation of PMNs into the lung is dependent on a complex cascade of events that includes the local production of chemokines. Interestingly, neonates are protected from lung injury after zymosan-induced sepsis. The authors hypothesized that this protection was caused by either altered PMN function or diminished lung chemokine production compared with the adult. METHODS: Sepsis was induced in neonatal and adult rats by an intraperitoneal injection of zymosan. Animals were killed 24 hours later and lungs examined for PMN accumulation and function, chemokine production, and lung injury. RESULTS: Septic neonates (SN) were protected from pulmonary edema when compared with septic adults (SA). Lung PMN number and chemokine (MIP-2) production increased in both septic neonates and adults when compared with vehicle (V) treated animals. Conversely, PMN function was decreased significantly in neonates when compared with adults. CONCLUSIONS: Despite equivalent lung PMN accumulation and chemotactic protein production, PMN function and lung injury in septic neonates was diminished when compared with that of adults. These findings suggest that neonates may be relatively protected from sepsis-induced lung injury caused by immature PMN function.

Animals↗
PubMed2002

The injured child is resistant to multiple organ failure: a different inflammatory response?

BACKGROUND: Although postinjury multiple organ failure (MOF) is a well-described phenomenon in adults, the incidence of this syndrome in children is unknown. The purpose of this study was to describe the incidence, course, and severity of pediatric postinjury MOF. We hypothesized that the incidence and severity of postinjury MOF in children would be less when compared with adults. METHODS: Patients were retrospectively identified from the trauma registry of a regional pediatric trauma center and an adult Level I trauma center with pediatric commitment for a 3-year period. All trauma patients less than 16 years old who survived for longer than 24 hours and had an Injury Severity Score > 15 were eligible. An accepted MOF score was used. Categorical variables were compared by chi2 and continuous variables by t test. A value of p< 0.05 was considered statistically significant. RESULTS: Of 534 patients identified, 334 (63%) were admitted for evaluation of isolated head injury and excluded from further analysis. The rate of postinjury MOF in children was found to be only 3%, with a low (17%) mortality when compared with historical adult data (50%). CONCLUSION: The incidence of postinjury MOF in the child is less than in the adult, given equivalent injury severity. These observations solidify the contention that postinjury MOF is rare in children, and is less severe when it occurs. Delineating the mechanism(s) whereby children are protected from postinjury MOF may provide insight into the development of strategies to prevent MOF in other age groups as well as various disease states.

Adolescent↗
PubMed2002

Neutralization of IL-18 attenuates lipopolysaccharide-induced myocardial dysfunction.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) have been implicated in cardiac dysfunction during endotoxemia. Because IL-18 is a proinflammatory cytokine known to mediate the production of TNF-alpha and IL-1beta and to induce the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), we hypothesized that neutralization of IL-18 would attenuate lipopolysaccharide (LPS)-induced cardiac dysfunction. Mice (C57BL/6) were injected with LPS (0.5 mg/kg ip) or vehicle (normal saline), and left ventricular developed pressure (LVDP) was determined by the Langendorff technique. LVDP was depressed by 38% at 6 h after LPS. LPS-induced myocardial dysfunction was associated with increased myocardial levels of TNF-alpha and IL-1beta as well as increased expression of ICAM-1/VCAM-1. Pretreatment with neutralizing anti-mouse IL-18 antibody attenuated LPS-induced myocardial dysfunction (by 92%) and was associated with reduced myocardial IL-1beta production (65% reduction) and ICAM-1/VCAM-1 expression (50% and 35% reduction, respectively). However, myocardial TNF-alpha levels were not influenced by neutralization of IL-18. In conclusion, neutralization of IL-18 protects against LPS-induced myocardial dysfunction. IL-18 may mediate endotoxemic myocardial dysfunction through induction of and/or synergy with IL-1beta, ICAM-1, and VCAM-1.

Animals↗
PubMed2002

ICAM-1 and VCAM-1 mediate endotoxemic myocardial dysfunction independent of neutrophil accumulation.

Both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been implicated in neutrophil-mediated lung and liver injury during sepsis. However, the role of these adhesion molecules as well as the contribution of neutrophils in myocardial dysfunction during sepsis remains to be determined. The purpose of this study was to examine the role of ICAM-1, VCAM-1, and neutrophils in lipopolysaccharide (LPS)-induced myocardial dysfunction. Mice were subjected to LPS (0.5 mg/kg ip) or vehicle (normal saline), and left ventricular developed pressure (LVDP) was determined by the Langendorff technique. LVDP was depressed by nearly 40% at 6 h after LPS. Immunofluorescent staining revealed a temporal increase in myocardial ICAM-1/VCAM-1 expression and neutrophils after LPS. Antibody blockade of VCAM-1 reduced myocardial neutrophil accumulation and abrogated LPS-induced cardiac dysfunction. Antibody blockade or absence of ICAM-1 (gene knockout) also abrogated LPS-induced cardiac dysfunction but did not reduce neutrophil accumulation. Neutrophil depletion (vinblastine or antibody) did not protect from LPS-induced myocardial dysfunction. Our results suggest that although endotoxemic myocardial dysfunction requires both ICAM-1 and VCAM-1, it occurs independent of neutrophil accumulation.

Animals↗
PubMed2002

IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia.

The influx of neutrophils into tissues in response to inflammatory stimuli involves C-X-C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro, but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C-X-C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blocked by IL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1beta that was decreased by Il-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS- treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1beta and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.

Animals↗