Document 0781
 DOCN  M94B0781
 TI    Interleukin-6 and the lung.
 DT    9412
 AU    Zitnik RJ; Elias JA; Dept. of Internal Medicine, Yale Univ. Sch. of
       Medicine, New; Haven, CT
 SO    Lung Biol Health Dis; 61:229-80 1993. Unique Identifier : AIDSLINE
       ICDB/94606665
 AB    Interleukin-6 (IL6) is a pleiotropic cytokine produced by a wide variety
       of cells, including many of the major cells in the lung, and in response
       to a broad spectrum of stimuli (eg, viral infection, bacterial
       endotoxin, agonists of cAMP, PKC, and calcium 2nd-messenger systems).
       Regulation of IL6 production is complex and can occur at the level of
       both gene transcription and mRNA degradation. The biological effects of
       IL6 are protean, and newly discovered activities continue to be
       described. IL6 production and activities are reviewed as follows: the
       IL6 protein (structure, molecular heterogeneity, and structure-function
       analysis), structure and regulation of the IL6 gene, the IL6 receptor,
       biological effects of IL6 (B-cell and T-cell effects, plasmacytoma and
       hybridoma growth, acute-phase response, hematopoiesis, and endocrine,
       neurobiologic, and cutaneous effects), IL6 in human homeostasis (acute
       inflammatory disorders, trauma and surgery, chronic inflammatory
       disorders, neoplastic disorders, transplant rejection, and HIV and
       Kaposi's sarcoma), and IL6 in the lung. IL6 causes disease by three
       major mechanisms: (1) IL6 can be overproduced, causing disease as a
       direct result of its systemic effects; (2) IL6 can be elevated as a
       protective reaction to stress, injury, or infections; and (3) IL6 may
       function as a part of dysregulated autocrine and paracrine feedback
       loops in chronic inflammatory disease and neoplastic disorders. In the
       pathogenesis of several neoplastic disorders, the effects of IL6 are
       mediated principally through two major mechanisms: some tumors
       constitutively produce large amounts of IL6, and the oversecreted
       cytokine produces the systemic manifestations of the tumor; other tumors
       constitutively produce and proliferate in response to IL6. The autocrine
       or paracrine (or both) effects of IL6 on the tumor are responsible for
       stimulating tumor cell proliferation and induction of the malignant
       phenotype. Hematological malignancies (multiple myeloma, leukemias, and
       lymphomas) and solid tumors are discussed. Several questions remain to
       be answered concerning IL6 and its role in the lung. Particular
       attention needs to be directed toward determining whether dysregulated
       autocrine or paracrine IL6 feedback loops play an important role in the
       pathogenesis of diseases such as sarcoidosis, asthma, hypersensitivity
       pneumonitis, allograft rejection, and lung cancer. (247 Refs)
 DE    Cell Division  Gene Expression Regulation  Human
       Interleukin-6/GENETICS/*METABOLISM  Lung/*METABOLISM  Lung
       Diseases/METABOLISM  Phenotype  RNA, Messenger/METABOLISM
       Transcription, Genetic  MONOGRAPH

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