Effect of Dexamethasone on Lymphocyte Subpopulations in Premature Infants with Bronchopulmonary Dysplasia

Abstract

OBJECTIVE:This study was designed to determine the effect of dexamethasone treatment on peripheral blood lymphocyte counts and subpopulations in premature infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN:Peripheral blood lymphocyte subpopulations in 12 premature infants with BPD were analyzed before treatment with a 6-week course of dexamethasone (day 0), on days 3 and 10 of treatment, and 2 weeks after discontinuing dexamethasone therapy (day 56). Lymphocyte immunophenotypes were determined using direct two-color immunofluorescent staining followed by flow cytometry. RESULTS:The percentage of lymphocytes was significantly lower on days 3 (17.55 Ϯ 2.55) and 10 (20 Ϯ 11.8) of dexamethasone therapy compared with before (30.36 Ϯ 6.41) or after treatment. The percentage of T cells was significantly lower on days 3 and 10 of dexamethasone therapy (mean Ϯ SEM; 58.09 Ϯ 1.93 and 60.09 Ϯ 2.47, respectively) compared with before (67.09 Ϯ 4.24) or after treatment. The absolute number of T cells was significantly lower on day 10 of therapy. The percentage of CD4 ϩ cells was significantly lower on days 3 (38.91 Ϯ 2.49) and 10 (40.45 Ϯ 2.24) of therapy, and this decrease persisted after dexamethasone was stopped (36.73 Ϯ 3.41). The absolute number of CD4 cells was significantly lower on day 10 (1328 Ϯ 216) of therapy and reached a nadir on day 56 (1143 Ϯ 106). Similarly, the CD4/CD8 ratio was also significantly lower on days 3 and 10 of treatment (1.56 Ϯ 0.18 and 1.64 Ϯ 0.14, respectively) and reached a nadir on day 56 (1.04 Ϯ 0.13). CONCLUSION:Dexamethasone significantly reduced the percentage and absolute number of lymphocytes, T cells, and CD4 cells, as well as the CD4/CD8 ratio. A reduction in CD4 cells and in the CD4/CD8 ratio persisted 2 weeks after dexamethasone therapy was stopped. In contrast, the absolute number of B cells increased transiently, and CD8 cells were unaffected by dexamethasone. This alteration in lymphocyte subpopulations may help account for the clinically beneficial anti-inflammatory effect of dexamethasone in the treatment of BPD complicated by respiratory failure. The dexamethasone-induced decrease in CD4 cells may also increase the susceptibility of these infants to infection.Bronchopulmonary dysplasia (BPD) is a chronic lung disease associated with mechanical ventilation in premature infants and a common cause of morbidity in the neonatal intensive care unit. The incidence of BPD is Յ40% among infants with respiratory distress syndrome who require mechanical ventilation. 1 Treatment with intravenous dexamethasone has been shown to shorten the duration of mechanical ventilation in premature infants, 2 and to improve pulmonary function. 3 However, dexamethasone therapy has many potential side effects in premature infants, including hyperglycemia, 4 hypertension, 5 cardiomyopathy, 6 adrenal suppression, 7-9 and gastrointestinal bleeding. 10 Dexamethasone has been shown to cause neutrophilia and eosinopenia 11,12 in addition to inhibition of colony formation of the hematopoietic progenito...

Inflammatory Mediators in the Immunobiology of Bronchopulmonary Dysplasia

“…This alteration in lymphocyte subpopulations may account for the clinically beneficial anti-inflammatory effect of dexamethasone in the treatment of BPD. It may also increase the susceptibility of these infants to infection, especially Candida sepsis [182,183].…”

Effect of Dexamethasone on B7 Regulation and T Cell Activation in Neonates and Adults

“…Dexamethasone may directly inhibit T cell proliferation (7), induce apoptosis (8), promote long-lasting changes in the T cell receptor v␤ repertoire (9), or decrease the CD4/CD8 ratio in infants with BPD (10). Dexamethasone also influences gene expression of cytokines and various functions of antigen pre-senting cells (APC), including B cells, dendritic cells, and monocytes/macrophages (11)(12)(13).…”

Lymphocyte Subpopulations in Bronchopulmonary Dysplasia

“…In the study reported here we found that the absolute number of lymphocytes was lower among infants with RDS who developed BPD compared with those who did not over the first 2 weeks of life and that the percentage and absolute number of CD4 + T cells were similarly affected. Parimi et al 11 have reported that premature infants given a 6-week course of dexamethasone had suppressed lymphocyte percentage and number and reduced CD4 + T cell percentage and number after 3 days of treatment compared with baseline values. Our study suggests that low lymphocyte numbers, especially CD4 + T cell numbers, may be intrinsically linked with susceptibility to BPD.…”

“…10 Conversely but interestingly, postnatal dexamethasone treatment of premature infants with BPD significantly decreases the percentage and absolute number of lymphocytes, T cells, specifically CD4 + T cells, and therefore the CD4 + /CD8 + ratio. 11 In addition, postnatal dexamethasone treatment in BPD increases B cells transiently and does not affect CD8 + T cells. However, there is little information on alterations in the lymphocyte subpopulations that might characterize the development of BPD, especially in the absence of clinical infection.…”