INCREASED RELEASE OF INTERLEUKIN-1-BETA, INTERLEUKIN-6, AND TUMOR-NECROSIS-FACTOR-ALPHA BY BRONCHOALVEOLAR CELLS LAVAGED FROM INVOLVED SITES IN PULMONARY TUBERCULOSIS

Mycobacterium tuberculosis and its components have been shown to stimu late mononuclear phagocytes in vitro to release interleukin-1 beta (IL -1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 ( IL-6). Animal models of tuberculosis (TB) also demonstrate the presenc e of cytokines in granulomas. We hypothesized that bronchoalveolar rav age (BAL) cells from patients with pulmonary TB would have increased s pontaneous release of IL-1 beta, IL-6, and TNF-alpha and would have a concomitant alveolitis. We performed BAL on 26 patients with active TB and on six normal volunteers. BAL fluid from radiographically involve d and uninvolved sites was evaluated separately for cell types and the spontaneous release of cytokines. The alveolar inflammation in involv ed sites was characterized by an increase in lymphocytes (miliary TB, 38 +/- 10%; involved sites, 22 +/- 4%; uninvolved sites, 13 +/- 2%; no rmal, 5 +/- 2%) and neutrophils (involved sites, 21 +/- 7%; uninvolved sites, 3 +/- 2%). There was a significant increase in the spontaneous release of IL-1 beta (501 +/- 280 pg/ml), TNF-alpha (782 +/- 165 pg/m l), and IL-6 (473 +/- 157 pg/ml) from involved sites of TB patients th at was 5- to 20-fold greater than uninvolved sites, normal controls, o r miliary TB. Northern analysis revealed increased gene expression of IL-1 beta, TNF-alpha, and IL-6 from the involved sites from two patien ts with TB compared with two negative controls. We conclude that BAL c ells, especially alveolar macrophages, are activated in the alveolar i nflammation of active TB and spontaneously release increased quantitie s of IL-1 beta, IL-6, and TNF-alpha, and that these cytokines are like ly to be involved in directing granuloma formation and control of M. t uberculosis infection.