- Email: [email protected]
210 Immunologic changes reflecting disease activity in silicosis
209
210
ANALYTICAL AND FUNCTIONAL ASSESSMENT OF LYMPHOID ?XLLS WITHIN MARINE LUNG. K Nuntirooj, ND, BE Boselka, PhD, RD deShazo, MD, and JE Salvaggio & New Orleans, LA Recent studies indicate that pulmonary lymphoid (Ly) effector cells originate at sites distant from the lung, This new data concerns numerical and functional properties of lung Ly populations among nonimmunized mice. Flow cytometric analysis of Ly cells isolated from lung tissue by collagenase digestion revealed 47% T-lymphocytes (helper:suppressor ratio 3.5), < 10% B-cells, 25% Ia+ cells, 23% SIg+ cells and 6% natural killer (HK) cells. Lung T-cells did not respond to Con-A stimulation without prior depletion of macrophages (MO). Lung cells exhibited significant NE activity in a tumor target cell Cr release assay. Nylon wool depletion of adherent cells and fractionation of the lung cells on percoll gradients resulted in enhanced activity. NK activity was significantly increased by poly I:C injections (10.7% vs 36.1% lysis) or by in vitro treatment of the lung cells with interferon (2.2% vs 27.3% lysis). Inclusion of < 80% lavage cells to the HR assay did not affect tumor cell lysis: > 80% MO resulted in reduction of NR activity (4.5% vs 2.0% lysis). Preincubation of alveolar MO (7%) with spleen cells for 18 hrs produced a notable but nonsignificant reduction of tumor cell lysis. Together these data indicate that normal lung contains a population of Ly cells quantitatively and qualitatively comparable to those found in the spleen. These studies form a basis for investigation of local pulmonary cellular reactions in murine models of immunologically-induced lung disease.
IMMUNOLQGIC CHANGES REFLECTING DISEASE ACTIVITY IN SILICOSIS. RP Stankus, Ph.D., M.D. and JE Salvaggfo, M.D. New Orleans, Louisiana Silicosls is a chronic fibrosing pulmonary disease with protean manifestations-of immunologic aberration. Here we report our observations on bronchopulmonary (BP) lavage fluid changes in human and experimental disease, In an animal model of experimental silicosis, adult, New Zealand white rabbits are exposed to free, crystalline silica via the respiratory While multiple humoral and tract route. cellular immune alterations occur, perhaps the most clinically relevant change is an increase in BP lavage fluid beta-glucuronidase activity. All (50) silica-exposed rabbits, examined as early as 1 month and as long as 24 months after exposure, demonstrate increased enzyme secretion (4-10 times greater than normal control values). Increased lavage fluid enzyme activity is associated with pulmonary histopathologic changes resembling‘those seen in human Elevated enzyme activity does not silicosls. occur in animals similarly exposed to either a commercial silica substitute or particulate, When compared with a control latex particles. population, human subjects with simple or complicated silicosis also have increased levels of beta-glucuronidase in BP lavage fluids. Lavage fluids from subjects with sarcoidosis do not have increased enzyme activity. these findings support the use of Collectively, beta-glucuronidase levels in BP lavage fluids as a marker of disease activity in silicosis and suggest a role for macrophage activation in disease pathogenesis.
2 11
ILD.. D. German., San Francisco, California. The purpose of this study was to determine the effect of TAO-methylprednisolone (MP) regimens on the incidence of corticosteroid induced side effects. Retrospective analysis was performed on the charts of 29 adult chronic steroid deaendent asthmatics on regimens of TAO-MP. These 29 met our criteria of a minimum of one year on TAO-MP and at least 6-12 months on daily or alternate day corticosteroids before TAO-MP was instituted. Charts were reviewed for 9 known corticosteroid (CS) side effects, all previously identified side effects were excluded. Charts were also reviewed for TAO dose, MP dose, and dose/duration on CS therapy before TAO-MP regimen began. Patients on TAO at an average dose of 250 mg/d were able to wean to an average MP dose of 10.8mg every other day from an average CS dose of 21 mg every other day before TAO. In spite of lower MP doses on TAO we found that 35% showed an increase in CS induced side effects, some (3) had more than Three patients developed cataracts 1 side effect. (lo%), 3 became Cushingoid (lo%), 2 became hypertensive(6.8%), 1 developed diabetes(3%), 1 had a psychotic episode (3%), and 1 patient (3%) developed TB and had a spinal compression fracture. 60% of these patients were on 8 mg, or less of MP on an alternate day basis. lnre found that in this group of 29 chronic steroid dependent asthmatics the incidence of corticosteroid related side effects was increased on TAOfJ[s;egimens despite a reduction in corticosteroid
212
157
CORTICOSTEROIDS AND MONOCYTE ACTIVATION IN BRONCHIAL ASTHMA. W. Gin, M.B., Ch.E., and A.B. Kay, M.D., Ph.D., London, U.K. We have examined the effect of corticosteroids on the expression of monocyte IgG (Fc) and complement (C) receptors using the rosette technique. The percentage of IgG (Fc) and C rosettes on peripheral blood monocyres from 31 asthmatics receiving inhaled therapy alone, but no oral corticosteroids, was srgnificantly increased Ip
210
ANALYTICAL AND FUNCTIONAL ASSESSMENT OF LYMPHOID ?XLLS WITHIN MARINE LUNG. K Nuntirooj, ND, BE Boselka, PhD, RD deShazo, MD, and JE Salvaggio & New Orleans, LA Recent studies indicate that pulmonary lymphoid (Ly) effector cells originate at sites distant from the lung, This new data concerns numerical and functional properties of lung Ly populations among nonimmunized mice. Flow cytometric analysis of Ly cells isolated from lung tissue by collagenase digestion revealed 47% T-lymphocytes (helper:suppressor ratio 3.5), < 10% B-cells, 25% Ia+ cells, 23% SIg+ cells and 6% natural killer (HK) cells. Lung T-cells did not respond to Con-A stimulation without prior depletion of macrophages (MO). Lung cells exhibited significant NE activity in a tumor target cell Cr release assay. Nylon wool depletion of adherent cells and fractionation of the lung cells on percoll gradients resulted in enhanced activity. NK activity was significantly increased by poly I:C injections (10.7% vs 36.1% lysis) or by in vitro treatment of the lung cells with interferon (2.2% vs 27.3% lysis). Inclusion of < 80% lavage cells to the HR assay did not affect tumor cell lysis: > 80% MO resulted in reduction of NR activity (4.5% vs 2.0% lysis). Preincubation of alveolar MO (7%) with spleen cells for 18 hrs produced a notable but nonsignificant reduction of tumor cell lysis. Together these data indicate that normal lung contains a population of Ly cells quantitatively and qualitatively comparable to those found in the spleen. These studies form a basis for investigation of local pulmonary cellular reactions in murine models of immunologically-induced lung disease.
IMMUNOLQGIC CHANGES REFLECTING DISEASE ACTIVITY IN SILICOSIS. RP Stankus, Ph.D., M.D. and JE Salvaggfo, M.D. New Orleans, Louisiana Silicosls is a chronic fibrosing pulmonary disease with protean manifestations-of immunologic aberration. Here we report our observations on bronchopulmonary (BP) lavage fluid changes in human and experimental disease, In an animal model of experimental silicosis, adult, New Zealand white rabbits are exposed to free, crystalline silica via the respiratory While multiple humoral and tract route. cellular immune alterations occur, perhaps the most clinically relevant change is an increase in BP lavage fluid beta-glucuronidase activity. All (50) silica-exposed rabbits, examined as early as 1 month and as long as 24 months after exposure, demonstrate increased enzyme secretion (4-10 times greater than normal control values). Increased lavage fluid enzyme activity is associated with pulmonary histopathologic changes resembling‘those seen in human Elevated enzyme activity does not silicosls. occur in animals similarly exposed to either a commercial silica substitute or particulate, When compared with a control latex particles. population, human subjects with simple or complicated silicosis also have increased levels of beta-glucuronidase in BP lavage fluids. Lavage fluids from subjects with sarcoidosis do not have increased enzyme activity. these findings support the use of Collectively, beta-glucuronidase levels in BP lavage fluids as a marker of disease activity in silicosis and suggest a role for macrophage activation in disease pathogenesis.
2 11
ILD.. D. German., San Francisco, California. The purpose of this study was to determine the effect of TAO-methylprednisolone (MP) regimens on the incidence of corticosteroid induced side effects. Retrospective analysis was performed on the charts of 29 adult chronic steroid deaendent asthmatics on regimens of TAO-MP. These 29 met our criteria of a minimum of one year on TAO-MP and at least 6-12 months on daily or alternate day corticosteroids before TAO-MP was instituted. Charts were reviewed for 9 known corticosteroid (CS) side effects, all previously identified side effects were excluded. Charts were also reviewed for TAO dose, MP dose, and dose/duration on CS therapy before TAO-MP regimen began. Patients on TAO at an average dose of 250 mg/d were able to wean to an average MP dose of 10.8mg every other day from an average CS dose of 21 mg every other day before TAO. In spite of lower MP doses on TAO we found that 35% showed an increase in CS induced side effects, some (3) had more than Three patients developed cataracts 1 side effect. (lo%), 3 became Cushingoid (lo%), 2 became hypertensive(6.8%), 1 developed diabetes(3%), 1 had a psychotic episode (3%), and 1 patient (3%) developed TB and had a spinal compression fracture. 60% of these patients were on 8 mg, or less of MP on an alternate day basis. lnre found that in this group of 29 chronic steroid dependent asthmatics the incidence of corticosteroid related side effects was increased on TAOfJ[s;egimens despite a reduction in corticosteroid
212
157
CORTICOSTEROIDS AND MONOCYTE ACTIVATION IN BRONCHIAL ASTHMA. W. Gin, M.B., Ch.E., and A.B. Kay, M.D., Ph.D., London, U.K. We have examined the effect of corticosteroids on the expression of monocyte IgG (Fc) and complement (C) receptors using the rosette technique. The percentage of IgG (Fc) and C rosettes on peripheral blood monocyres from 31 asthmatics receiving inhaled therapy alone, but no oral corticosteroids, was srgnificantly increased Ip