INTERLEUKIN-12 AT THE SITE OF DISEASE IN TUBERCULOSIS

Interleukin 12 (IL-12), a heterodimeric cytokine composed of p40 and p 35 chains, has potent immunologic effects in vitro. We used tuberculou s pleuritis as a model to study the immunoregulatory potential of IL-1 2 in vivo at the site of human infectious disease. Messenger RNAs for p40 and p35 were detected in pleural fluid from six of six patients by reverse-transcription polymerase chain reaction. By using an ELISA th at detected both free p40 and heterodimeric IL-12, we found that mean concentrations were 585+/-89 pg/ml in pleural fluid of patients with t uberculous pleuritis, which were significantly higher than those in se rum of the same patients (54+/-36 pg/ ml), or in malignant pleural eff usions (123+/-35 pg/ml). By using an ELISA specific for heterodimeric IL-12, we found that mean concentrations in pleural fluid of patients with tuberculous pleuritis were 165+/-28 pg/ml and undetectable in ser um of the same patients, or in malignant pleural effusions. Bioactive IL-12 was detectable in five of five supernatants of pleural fluid cel ls stimulated with Mycobacterium tuberculosis. Addition of anti-IL-12 antibodies suppressed proliferative responses of pleural fluid cells t o M. tuberculosis by 36+/-7%. These data indicate that IL-12 may play a role in the human immune response to infectious agents in vivo. We h ypothesize that IL-12 contributes to the antimycobacterial immune resp onse by enhancing production of interferon-gamma, facilitating develop ment of Th1 cells and augmenting cytotoxicity of antigen-specific T ce lls and natural killer cells.