Defective leukotaxis in monocytes from patients with pulmonary tuberculosis.
Because the accumulation of macrophages and their precursors, peripheral blood monocytes, in foci of infection is an important feature of the host reponse to mycobacterial challenge, the leukotactic responsiveness of monocytes from patients with active tuberculosis was evaluated. With a double-filter, in vitro technique, defective leukotaxis was demonstrated in monocytes from 19 of 20 untreated patients, whereas normal leukotactic responses were found in monocytes from 11 of 15 patients with chronic, nontuberculous pulmonary inflammatory diseases. This defect may be related to increased activity of a naturally occurring, heat-stable plasma substance with a molecular mass of approximately 2.3 x 10(5) daltons that inhibited leukotactic responsiveness. Monocyte leukotaxis improved and the leukotactic inhibitory activity of plasma disappeared in most patients while they were on therapy; these phenomena were unrelated to bacteriologic conversion or resolution of symptoms. In vitro studies with isoniazid, ethambutol, and rifampin excluded a direct effect of these drugs or their metabolites on monocytes or on the leukotactic inhibitor in plasma. Thus, defective leukotaxis of monocytes in patients with pulmonary tuberculosis may be an epiphenomenon of the local tissue reaction.
D000293:Adolescent; D000328:Adult; D000368:Aged; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002908:Chronic Disease; D004306:Dose-Response Relationship, Immunologic; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D007538:Isoniazid / Q000627:therapeutic use; D008171:Lung Diseases / Q000276:immunology; D008222:Lymphokines / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D012293:Rifampin / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*; D015054:Zymosan / Q000276:immunology
D008222:Lymphokines; D004977:Ethambutol; D015054:Zymosan; D007538:Isoniazid; D012293:Rifampin