Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Initial Cell Counts

Association of Activated Cytolytic Lung Lymphocytes with Response to Prednisone Therapy: Initial Cell CountsInitial Cell Counts
The median total and median differential initial cell counts of IPF patients and of normal subjects are shown in Table 1. These data demonstrate increased total cell numbers and percentages of polymorphonuclear lymphocytes in BAL fluid of patients with IPF. Some patients with IPF also had increased percentages of lymphocytes. The above findings are consistent with previous reports of IPF alveolitis.

Intitial Immunologic Studies
The results of initial CDCMC assays on lymphocytes obtained from BAL fluid of IPF patients are shown in Figure 2 (closed symbols, panel A). CDCMC was detected in the BAL fluid of four of ten patients with IPF. In contrast, cytolytic activity was not detected in BAL fluid of normal subjects (n = 8, CDCMC of BAL fluid = 0). Lectin-dependent cytotoxicity was observed in the peripheral blood of four patients with IPF (Fig 2, panel B, closed symbols); only two of whom had cytolytic activity in BAL fluid (Fig 2). Normal subjects had no detectable lectin-dependent cytolytic activity in peripheral blood (n = 8; CDCMC activity of peripheral blood = 0). Reading here

Longitudinal Studies of Pulmonary Function and Cytolytic Lymphocyte Activity
Serial PFTs were performed on all ten IPF patients. Diffusing capacity for carbon monoxide (Dsb) and VC were measured before and during prednisone treatment (Fig 1). Four of the ten IPF patients had improved pulmonary function following therapy (Fig 1). Of importance, these latter patients were the subjects who had initial CDCMC activity in BAL fluid (Fig 2). The mean±SEM increase in diffusing capacity was 30 ±2 percent in these latter patients. The improvement in PFTs was associated with improved dyspnea and exercise tolerance (ascertained by clinical history). In contrast, patients without initial CDCMC in BAL fluid (n = 6) did not have a significant increase in diffusing capacity (Fig 1 and 2). The patients with increased pulmonary function also had decreased or absent CDCMC in subsequent analysis of BAL fluid following treatment (Fig 2, open symbols). Patients without CDCMC in intial studies of BAL fluid continued to lack cytolytic activity after prednisone treatment (Fig 2, open symbols). Patients with activity in peripheral blood only did not exhibit improvement in pulmonary function with therapy (Fig 2 and 3). Total and differential cell count data from serial BAL fluid studies are shown in Figure 3. None of these measurements was consistently associated with improved pulmonary function or cytolytic lymphocyte activity.
Table 1—Total and Differential Cell Counts in BAL Fluid

Subjects N Total Cells/ml BALx 10“ Differential Cell Counts in BAL (%)
M L P
Idiopathicpulmonary

fibrosis

10 1.1(0.2-9.0) 57(14-98) 23(14-49) 24(0-72)
Normal 8 0.6(0.4-0.8) 80(78-82) 20(17-22) 0(0-2)

 

Figure 2. Longitudinal studies of cytolytic lymphocyte activity in BAL fluid (panel A) and peripheral blood (panel B) of patients with IPF. Cytolytic activity was assessed by the CDCMC assay. Three patients with significant initial BAL CDCMC activity had no CDCMC activity during prednisone treatment. A fourth patient with initial CDCMC activity (•) had decreased CDCMC activity following treatment at one-half the prescribed dose of prednisone. The experimental values are represented by the identical symbols as in Figure 1. Closed symbols = pretreatment; open symbols = posttreatment.

Figure 2. Longitudinal studies of cytolytic lymphocyte activity in BAL fluid (panel A) and peripheral blood (panel B) of patients with IPF. Cytolytic activity was assessed by the CDCMC assay. Three patients with significant initial BAL CDCMC activity had no CDCMC activity during prednisone treatment. A fourth patient with initial CDCMC activity (•) had decreased CDCMC activity following treatment at one-half the prescribed dose of prednisone. The experimental values are represented by the identical symbols as in Figure 1. Closed symbols = pretreatment; open symbols = posttreatment.

Figure 3. Longitudinal studies of BAL fluid ceil contents. Cells were harvested from BAL fluid and processed as described (Materials and Methods). Cell content values before therapy (closed symbols) and during therapy (open symbols) are represented by the same symbols as Figures 1 and 2.

Figure 3. Longitudinal studies of BAL fluid ceil contents. Cells were harvested from BAL fluid and processed as described (Materials and Methods). Cell content values before therapy (closed symbols) and during therapy (open symbols) are represented by the same symbols as Figures 1 and 2.

Category: Pulmonary Fibrosis

Tags: bronchoscopy, lung lymphocytes, peripheral blood, pulmonary fibrosis, pulmonary function