title: Interleukin 12 at the site of disease in tuberculosis.
abstract: Interleukin 12 (IL-12), a heterodimeric cytokine composed of p40 and p35 chains, has potent immunologic effects in vitro. We used tuberculous pleuritis as a model to study the immunoregulatory potential of IL-12 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 that detected both free p40 and heterodimeric IL-12, we found that mean concentrations were 585 +/- 89 pg/ml in pleural fluid of patients with tuberculous pleuritis, which were significantly higher than those in serum of the same patients (54 +/- 36 pg/ml), or in malignant pleural effusions (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 serum of the same patients, or in malignant pleural effusions. Bioactive IL-12 was detectable in five of five supernatants of pleural fluid cells stimulated with Mycobacterium tuberculosis. Addition of anti-IL-12 antibodies suppressed proliferative responses of pleural fluid cells to 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 hypothesize that IL-12 contributes to the antimycobacterial immune response by enhancing production of interferon-gamma, facilitating development of Th1 cells and augmenting cytotoxicity of antigen-specific T cells and natural killer cells.
authors.affiliation: Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Gong
authors.forename: S F
authors.initials: SF
authors.lastname: Wolf
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
authors.forename: P F
authors.initials: PF
authors.lastname: Barnes
mesh_terms: D001483:Base Sequence; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010994:Pleura / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D014396:Tuberculosis, Pleural / Q000276:immunology*
chemical_list: D007378:Interleukins; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma