DECREASED TOBACCO-GLYCOPROTEIN-INDUCED LYMPHOCYTE-PROLIFERATION IN-VITRO IN PULMONARY EOSINOPHILIC GRANULOMA

Pulmonary eosinophilic granuloma is a disorder caused by localized col lections of proliferating histiocytes in the lung. Little is known abo ut its etiology except that the majority (58 to 97%) of patients are c urrent or ex-smokers, making the potential etiologic role of tobacco p roducts an important area for research. Tobacco glycoprotein (TGP) is a potent immunostimulator that has been isolated from cigarette smoke. TOP-specific lymphocyte proliferation, and cytokine production in vit ro, were measured in three patients with pulmonary eosinophilic granul oma in remission and in three closely matched normal subjects with sim ilar smoking histories. One patient with eosinophilic granuloma of bon e and a matched control subject were also studied. Peripheral blood mo nonuclear cells were cultured with TGP, tile recall antigen streptokin ase (SK), and the mitogen concanavalin A (Con A). All three of the pat ients with pulmonary eosinophilic granuloma exhibited significant decr eases in lymphocyte stimulation to TGP, despite normal responses to SK and Con A. In contrast, the response of the patient with eosinophilic granuloma of bone was higher than her matched control. The mean respo nses of the patients with pulmonary eosinophilic granuloma to TGP was significantly lower than the mean of nondiseased smokers or of normal nonsmokers. Twenty-four-hour culture supernatants were collected and a ssayed for cytokine levels (IL-l, IL-2, and IL-6). TOP-stimulated IL-2 production was significantly lower in the patients with pulmonary eos inophilic granuloma than in the normal subjects, confirming the reduce d T-cell proliferative response. TG was found to be a very potent indu cer of IL-1 and IL-2, but there was no difference between patients and control subjects. These findings demonstrate that the lymphocyte prol iferation response of patients with pulmonary eosinophilic granuloma t o TGP is significantly different from the response of normal subjects or cigarette smokers without this disease, and they suggest that an al tered immune response to TGP may be involved in the pathogenesis of th e disease. However, the exact mechanisms by which tobacco might induce pulmonary eosinophilic granuloma remain to be established.