IL-13 and STAT6 signaling involve in low dose lipopolysaccharide induced murine model of asthma

BACKGROUND: We reported that level of lipopolysaccharide (LPS) exposure determined the type of airway inflammation in a murine model of asthma. OBJECTIVE: The purpose of this study is to evaluated the role of IL-13 in low dose LPS induced murine model of asthma using IL-13 and signal transducer and activator of transcription 6 (STAT6) deficient mice. METHODS: Mice were sensitized with an intranasal application of LPS-depleted ovalbumin (OA) and different doses of LPS (0.1 and 10 µg), and then challenged intranasally with OA alone. The phenotype changes between wild type (WT) and IL-13-/- mice and between WT and STAT6-/- mice were evaluated. RESULTS: We confirmed again that low and high dose LPS resulted in different phenotypes of murine asthma. In the present study, we observed that phenotypes of murine asthma induced by low dose LPS were abolished in the homozygous null mutation of the IL-13 and STAT6 gene. However, those changes were not shown in mice sensitized OA plus high dose LPS. CONCLUSION: IL-13 plays an important role in low dose LPS induced murine model of asthma. Our results provided a new insight in understanding of the potential role of IL-13 in innate immunity in human allergic asthma.

Clinical implication of serum TNF-alpha and IL-1beta measurement in patients with sepsis / 결핵

BACKGROUND: It is well known that when macrophages are stimulated with endotoxin, they produce a wide variety of cytokine mediators, including TNF-α and IL-1β. However, there is an alterationnin the macrophages responsiveness when they are challenged with repeated bouts of endotoxin, termed 'endotoxin tolerance' which is regarded as a self-protective phenomenon from continuous stimulation. In this study, endotoxin tolerance in the peripheral blood monocytes of sepsis patients was evaluated. METHODS: Fourteen patients with organism-documented sepsis were included. The severity of illness was evaluated by APACHE IIscore. Peripheral blood monocytes were isolated from the patients and diluted to 1×105/well. After stimulation with endotoxin(LPS of E. coli O114:B4, 100 ng/ml), they were incubated at 37℃ in 5% CO2 incubator for 24 hours. Supernatant was collected for the measurement of TNF-αand IL-1β with ELISA method. Peripheral blood monocytes of seven healthy volunteers were used as control. RESULTS: The APACHE IIscore(mean±SD) of the patients at the time of blood sampling was 12.2±5.7. The primary infection foci were urinary tract infection, pneumonia, subacute bacterial endocarditis, and catheter related infection, etc. The causative organisms were gram negative rods(10 cases), gram positive cocci(6 cases) with two cases of mixed infection. Serum TNF-α could be measured in 4 cases with 29.9±27.7 pg/ml. Serum IL-1β was measureable in only one patient. The TNF-α level of supernatant of cultured peripheral blood monocytes was 2,703±2,066 pg/ml in patients and 2,102±1,914 pg/ml in controls. The IL-1β level of supernatant was 884±1,050 pg/ml in patients and 575±558 pg/ml in controls. There was no difference of TNF-α and IL-1β level between patients and controls. CONCLUSION: We cannot prove the phenomenon of endotoxin tolerance in this study. Future study needs to be focused on the more severe sepsis patients who were taken for sampling earlier. Addition of serum to the culture medium could be an another valuable option for the success of this study.

Cardiorespiratory Responses of Pilots to Maximal Exercise Loading

BACKGROUND: To provide some fundamental physiological basis for the physical training of pilots to improve orthostatic intolerance, cardiorespiratory responses to the symptom-limited maximal exercise loading were studied in pilots and non-pilots, and the results were compared. METHOD: Cardiorespiratory reponses to the symptom-limited maximal exercise loading by Bruce protocol was studied in 11 pilots and 11 matched controls (non-pilots). RESULTS: Comparisons of various data at maximal exercise in the pilots with those in the controls revealed that RR, VE/M2, VE/VO2, VE/VCO2, VT/VC and VE/MVV as well as HR, VO2, O2 pulse and AT showed no significant difference. CONCLUSION: The fact that the aerobic power in the pilots is not superior to that in the controls seems to emphasisze the necessity of aerobic endurance training along with muscular strength training to improve orthostatic tolerance of pilots flying modern high-performance aircrafts.