Multiple activities of a cloned cell line mediating natural killer cell function.

A special class of immunologic cells can lyse or damage a variety of target cells, notably malignant cells in vitro. These cells have been called natural killer (NK) cells because lysis does not require deliberate immunization by tumor cells. Although these cells can be distinguished from conventional T cells, B cells, and phagocytic cells, they have been difficult to define. We describe a representative cloned cell line that was obtained by cloning Ig -Ly-5+ cells from spleen. This clone, Cl.Ly-1-2-NK-1+/11, displays Thy-1, Ly-5, Qat-4, Qat-5 and NK-1 cell surface antigens and lyses the NK-sensitive YAC-1 lymphoma cells, but does not lyse RL-12 cells, an NK-resistant lymphoma. In addition, this clone lysed the P815 mastocytoma, EL4 lymphoma, and lipopolysaccharide-activated B lymphocyte targets. This cloned population therefore combined information for a unique display of cell surface antigens and specialized function similar to "activated" NK cells. Because this cloned population forms conjugates with susceptible but not resistant target cells, it may prove useful to identify the structure of cell surface molecules that recognize foreign cells. Finally, cells of this clone also specificity lysed target cells coated by antibodies to determinants on the target cell surface, demonstrating that a single cloned cell population can mediate two specialized immunologic functions: antibody-dependent cellular cytotoxicity and NK cell lysis.

Increased immunoreactive erythropoietin in cord plasma and neonatal bilirubin production in normal term infants after labor.

The purpose of this investigation was to compare immunoreactive erythropoietin levels in umbilical cord plasma and neonatal bilirubin production in infants born of normal women who delivered with or without labor. Two groups of term (38 to 42 weeks) singleton pregnancies were compared: 1) those delivered by repeat elective cesarean section without prior labor (N = 17), and 2) those delivered vaginally or by cesarean section after labor (N = 24). None of the infants was asphyxiated, and there was no difference in Apgar scores between the no-labor and labor groups. The cord plasma erythropoietin levels were lower in the infants of women who had repeat elective cesarean section without labor than in those whose mothers had labor before delivery (Wilcoxon rank sum test, P less than .025). The median erythropoietin for the no-labor group was 22.9 mU/mL compared with 38.8 mU/mL for the labor group. The pulmonary excretion rate of carbon monoxide (VeCO), an index of bilirubin production, for the no-labor group was 14.3 +/- 6.2 SD microL/kg per hour compared with 18.0 +/- 4.9 SD microL/kg per hour for the labor group (P less than .05). The hemoglobin concentration for the no-labor group was 16.0 +/- 1.5 SD g/dL compared with 17.7 +/- 2.2 SD g/dL for the labor group (P less than .05). The VeCO correlated with the hemoglobin concentration (N = 32, r = 0.37, P less than .05). The results of the present study suggest that labor is normally associated with increases in the cord plasma erythropoietin level.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary excretion of carbon monoxide in the human infant as an index of bilirubin production. IIc. Evidence for the possible association of cord blood erythropoietin levels and postnatal bilirubin production in infants of mothers with abnormalities of gestational glucose metabolism.

A total of 20 infants who had levels of erythropoietin (Ep), the major hormone regulating erythropoiesis, measured in their cord blood also had determinations of the pulmonary excretion rate of CO (VECO) performed, as an index of total bilirubin production. They were either infants of normal mothers or those of mothers with diabetes, gestational diabetes, and missed abnormalities of gestational glucose metabolism. The mean VECO (13.0 +/- 3.5 mu 1/kg/hr) and the mean Ep (20.0 +/- 9.7 SD mU/ml) of the infants with normal mothers (n = 9) were not different from the means previously established by our laboratories (13.9 +/- 3.5 SD mu 1/kg/hr, n = 20; and 23.7 +/- 12.8 SD mU/ml, n = 30, respectively); they were significantly lower than those of the infants of the abnormal mothers in this study. The 5 infants who had a cord blood Ep level greater than 50 mU/ml had a higher mean VECO, 27.8 +/- 7.1 mu 1/kg/hr, compared with 17.2 +/- 4.9 SD mu 1/kg/hr, of the six infants with cord blood Ep levels that were within 2 SD of the previously established normal mean cord blood Ep level (p less than .025). These data suggest that increased cord blood Ep levels and postnatal bilirubin production in infants whose mothers had abnormalities of gestational glucose metabolism are associated phenomena. Since polycythemia did not occur in these infants, ineffective erythropoiesis or mild, compensated hemolysis remains a likely cause of the increased total bilirubin production. In some cases, perinatal hypoxic stress may have affected the Ep response.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of steroid-dependent asthma with recombinant interferon-gamma.

We have recently reported that treatment of patients with severe atopic dermatitis with recombinant interferon-gamma (rIFN-gamma) resulted in clinical improvement as well as a reduction of circulating eosinophils. Since IgE-dependent late phase allergic reactions and eosinophilic infiltration are thought to play an important role in the pathogenesis of asthma, we conducted a two centre randomized double-blind placebo-controlled trial of rIFN-gamma in the treatment of steroid-dependent asthma. Patients were treated with daily subcutaneous injections of either 0.05 mg/m2 rIFN-gamma (n = 9) or placebo (n = 11) for 90 days. All patients completed the study without significant drug toxicity noted. Oral prednisone dose, forced expiratory volume in 1 second (FEV1), peak expiratory flow rates (PEFR) and circulating eosinophil counts were monitored throughout the trial. There was no significant difference between the two treatment groups in per cent reduction from baseline of daily prednisone (P = 0.51). There was also no significant difference between the two treatment groups in per cent change from baseline in FEV1 (P = 0.54) or in PEFR (P = 0.75). Total circulating eosinophil counts decreased by 31% in the rIFN-gamma group and increased by 8.5% in the placebo group (P = 0.09). We conclude that this treatment regimen was not effective in patients with steroid-dependent asthma.

Recombinant interferon gamma therapy for atopic dermatitis.

BACKGROUND: Atopic dermatitis is characterized by immunologic abnormalities including evidence for reduced interferon gamma production. Therapeutic options for treatment of atopic dermatitis are limited and unsatisfactory. Previous open trials have suggested efficacy for recombinant interferon-gamma (rIFN-gamma) in treatment of severe atopic dermatitis. We describe the results of treatment with rIFN-gamma, assessing clinical, immunologic, and laboratory safety parameters in 83 patients with moderate to severe atopic dermatitis. OBJECTIVE: Our purpose was to determine in a randomized, placebo-controlled, double-blind multicenter study the effects of recombinant human interferon gamma therapy in patients with atopic dermatitis. METHODS: Patients received 50 micrograms/m2 rIFN-gamma (n = 40) or placebo (n = 43) by daily subcutaneous injection for 12 weeks. Seventy-eight patients completed the treatment course; two patients receiving rIFN-gamma (one because of constitutional side effects) and three receiving placebo discontinued treatment before completion. Physician and patient overall response evaluations, clinical severity scores, body surface area involvement, and laboratory parameters were monitored throughout the trial. RESULTS: Patients in both treatment groups were similar except that the rIFN-gamma group was older and had a longer disease duration. Forty-five percent of rIFN-gamma-treated patients and 21% of placebo-treated patients achieved greater than 50% improvement in physicians' overall response evaluations (p = 0.016). As estimated by patients, responses also showed significant improvement in the rIFN-gamma group compared with the placebo group (53% vs 21%, p = 0.002). Significant reductions in erythema (p = 0.035) and in excoriations or erosions (p = 0.045) occurred in rIFN-gamma-treated patients. Other atopic symptoms such as conjunctivitis (p < 0.002) were also reduced in the rIFN-gamma group. Occasional headaches, myalgias, or chills occurred in 30% to 60% of rIFN-gamma-treated patients but were effectively prevented by pretreatment acetaminophen and by dosing at bedtime. Grade II granulocytopenia occurred in five rIFN-gamma patients but normalized with continued treatment. Reduction to alternate-day dosing was necessary for six patients in the rIFN-gamma group and two in the placebo group. Seven had mild elevations of hepatic transaminase levels that did not affect therapy. The mean eosinophil count was significantly reduced (p = 0.003), whereas a nonsignificant increase in serum IgE levels occurred in the active treatment group. CONCLUSION: This study demonstrated that rIFN-gamma given by daily subcutaneous injection over a 12-week period was safe, well accepted, and effective in reducing inflammation, clinical symptoms, and eosinophilia in severe atopic dermatitis.