Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

Evaluation of a new thin-walled endotracheal tube for use in children.

Conventional endotracheal tubes have high intrinsic resistive properties due to their high outer-to-inner diameter ratio. This has significant disadvantages in the treatment of the small neonatal or pediatric patient as work of breathing increases with decreasing internal radius. Diagnostic and therapeutic procedures, including suctioning, may be very difficult in patients with small endotracheal tubes. We therefore measured airway resistance and pressure differential during simulated mechanical ventilation using proximal and distal endotracheal tube flow transducers. Conventional and new, ultrathin-walled endotracheal tubes reinforced with flat stainless steel or a novel, crush-proof nickel-titanium alloy were compared using fixed ventilator settings. Ventilation through the ultrathin-walled tubes resulted in a significantly reduced airway resistance (p < or = 0.01). These new ultrathin-walled endotracheal tubes showed flow characteristics typical of much larger conventional endotracheal tubes: the 3.2-mm internal diameter had an airway resistance (Raw) of 36, while a standard 2.5-mm internal diameter endotracheal tube had a Raw of 146. Both endotracheal tubes have identical external diameters of 3.6 mm. We conclude that ultrathin-walled endotracheal tubes could have a significant role in the treatment of the ventilated child by facilitating interactive ventilation and maintenance of airway patency and may make procedures such as fiberoptic endoscopy and intrapulmonary ventilation using reverse-thrust catheters possible in the small child.

Intratracheal pulmonary ventilation provides effective ventilation in a near-drowning model.

Overdistension of the lungs from high inspiratory pressure is increasingly recognized as a major contributor to lung injury and worsening respiratory failure in the child who requires prolonged mechanical ventilation. Many modes of ventilation (such as high-frequency ventilation) have been introduced in an attempt to decrease this lung injury. Recently, a new mode of tracheal ventilation, intratracheal pulmonary ventilation (ITPV), has been described. By using a catheter positioned at the carina with continuous gas flow, it is possible to achieve effective ventilation at very low pressures. The purpose of this study was to evaluate the usefulness of ITPV in a near-drowning model. Ten domestic Yorkshire swine underwent arterial, venous, and pulmonary arterial catheter as well as tracheotomy placement. All animals received 13 mL/kg of fresh water intratracheally to induce a pulmonary injury. Six pigs were ventilated for 4 hours using ITPV; the other four pigs received conventional mechanical ventilation (CMV). Circulatory and ventilatory pressures, hemodynamic variables, arterial blood gases, and end-tidal CO2 were measured before lung injury and every 30 minutes thereafter. Both proximal and distal peak and mean airway pressures were measured. The animals were ventilated as needed to maintain the arterial blood gases in the normal range. The authors found the expected changes in pulmonary compliance, oxygen requirement, and airway pressure after inducement of lung injury. The six animals treated with ITPV had significantly lower airway pressures than those of controls. Peak inspiratory pressures with ITPV were 8.2 +/- 1.9 cm H2O versus 17.8 +/- 3.7 with CMV (P < .001). Distal mean airway pressures using ITPV were 2.3 +/- 0.1 cm H2O versus 9.0 +/- 3.2 with CMV (P < .01). With respect to hemodynamic variables, there were no differences between experimental and control animals. In conclusion, ITPV can afford effective ventilation in a near-drowning model of lung injury at airway pressures significantly lower than those required with CMV. ITPV could be a very valuable addition to the currently available methods of mechanical ventilation.

Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo.

The major regulator of circulating platelet levels is believed to be a cytokine termed thrombopoietin. It is thought to be a lineage-specific cytokine affecting the proliferation and maturation of committed cells resulting in the production of megakaryocytes and platelets. Despite considerable efforts by a number of laboratories, the unequivocal identification of thrombopoietin has proven elusive. Here we report the functional cloning of a murine complementary DNA encoding a ligand for the receptor encoded by the c-mpl proto-oncogene (c-Mpl). The encoded polypeptide has a predicted molecular mass of 35,000 (M(r) 35K). The protein has a novel two-domain structure with an amino-terminal domain homologous with erythropoietin and a carboxy-terminal domain rich in serine, threonine and proline residues and containing seven potential N-linked glycosylation sites. Intraperitoneal injections of mice with recombinant protein increase circulating platelet levels by greater than fourfold after 7 days. These results along with those presented in the accompanying report strongly suggest that the ligand for c-Mpl is thrombopoietin.