Superoxide dismutase (SOD) is supposed to be an effective agent for neutrophil-mediated inflammation in the area of critical medicine. We investigated the involvement of SOD in the regulation of neutrophil apoptosis. Exogenously added SOD effectively induced neutrophil apoptosis, and the fluorescence patterns determined using annexin-V and the 7-AAD were similar to those seen in Fas-mediated neutrophil apoptosis. Neutrophils are short-lived leukocytes that need to be removed safely by apoptosis. The clearance of apoptotic neutrophils from sites of inflammation is a crucial determinant of the resolution of inflammation. Catalase inhibited the neutrophil apoptosis and caspase-3 activation. Spontaneous apoptosis, hydrogen peroxide and anti-Fas antibody-induced apoptosis of neutrophils were accelerated in Down's syndrome patients, in whom the SOD gene is overexpressed. Hydrogen peroxide was thought to be a possible major mediator of ROS-induced neutrophil apoptosis in caspase-dependent manner. Neutrophil apoptosis represents a crucial step in the mechanism governing the resolution of inflammation and has been suggested as a possible target for the control of neutrophil-mediated tissue injury. SOD may be a potential inhibitory mediator of neutrophil-mediated inflammation.

Background: β₂-Adrenergic agonists play a pivotal role in the management of bronchial asthma. Although the major effect of short-acting β₂-agonists on the airway is relaxation of smooth muscles, they may also have several effects on surrounding immunomodulatory cells. Methods: We examined whether widely used short-acting β₂-agonists differ in their ability to modulate granulocyte functions, such as superoxide anion (O₂^–) production and degranulation. Results: Procaterol (PC), a full agonist, significantly inhibited both O₂^– production by granulocytes (neutrophils and eosinophils) and their degranulation at the clinically relevant concentrations, whereas salbutamol and tulobuterol (partial agonists) showed smaller effects. PC inhibited N-formyl methionyl-leucyl-phenylalanine-induced O₂^– production and peroxidase release, but failed to inhibit responses induced by phorbol 12-myristate 13-acetate and/or opsonized zymosan. Exposure to 5 × 10^–8M PC for 120 min resulted in approximately 50% inhibition of O₂^– production and degranulation of neutrophils. The effects of β₂-agonists were more obvious in neutrophils than in eosinophils. A selective β₂-receptor antagonist, ICI-118551, reversed the inhibitory effect of β₂-agonists (PC, salbutamol, tulobuterol B) on N-formyl methionyl-leucyl-phenylalanine-induced O₂^– production. Conclusions: These results suggest that β₂-agonists had an inhibitory effect on granulocyte functions, mainly mediated viareceptors and their efficacy. Our observations support that β₂-agonists with a rapid onset of action and high intrinsic efficacy (short-acting and full agonists) may be optimal for the rescue therapy against acute asthma attack and sedation of its airway inflammation in an early phase.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Background/Aims: Human pulmonary alveolar epithelial (A549) cells release interleukin-8 (IL-8) on stimulation by lipopolysaccharide (LPS) and α-toxin. We hypothesised that the perfluorocarbons (PFCs), perflubron and FC-84, would block stimulation of A549 cells by these toxins. Methods: The levels of IL-8 production in A549 cells were measured following exposure to toxins for 24 h with or without PFC. The amount of IL-8 released from A549 cells was measured by enzyme-linked immunosorbent assay, and the level of IL-8 mRNA was measured by real-time RT-PCR. Results: When stimulated with LPS or α-toxin, IL-8 release from A549 cells increased. There were no significant differences in level of IL-8 release between cells pre-incubated for 24 h with or without PFC after toxin stimulation for 24 h. When PFC was administered along with LPS stimulation, the level of IL-8 release was decreased (LPS control, 1,398 ± 110 pg/well; FC-84, 686 ± 50 pg/well; perflubron, 749 ± 137 pg/well; p < 0.05). Levels of IL-8 mRNA expression were significantly higher with than without LPS, and those with LPS and perflubron were significantly lower than those with LPS alone. Conclusions: The results show that PFCs block stimulation of A549 cells by LPS or α-toxin. PFC may be useful clinically in treatment of pulmonary inflammation in the alveolar space.