S Fujino, A Yokoyama, N Kohno and K Hiwada
Second Department of Internal Medicine, Ehime University, School of Medicine, Japan.

Interleukin 6 (IL-6) is a multifunctional inflammatory cytokine whose abnormal production has been implicated in a variety of diseases. Our previous study demonstrated that exudative pleural effusions contain a large amount of IL-6, and the levels of IL-6 in pleural effusion have diagnostic and pathophysiologic values. Although IL-6 is produced by a variety of cells, the origin of IL-6 in pleural effusion has not been determined clearly. We hypothesized that pleural mesothelial cells (PMCs) are an important source of IL-6 in pleural diseases. In this study, we tried to demonstrate whether PMCs could produce IL-6 and to characterize the modulation of its production. PMCs were established from patients with nonmalignant pleural effusion. Immunoreactive IL-6 could be detected in cultured supernatants of all PMCs from five patients, and all IL-6 detected in the supernatants were biologically active. IL-6 production was augmented by the addition of interleukin 1 alpha (IL-1 alpha) in a dose-dependent manner and suppressed by dexamethasone. Expression of IL-6 mRNA was spontaneously observed and was increased by IL-1 alpha. PMCs also expressed mRNA for IL-6 receptors gp80 and gpl30. Spontaneous cell growth and DNA synthesis of PMCs were inhibited by the addition of a neutralizing anti-IL-6 monoclonal antibody and were promoted by the addition of IL-6 to the culture. These results suggest that IL-6 is an autocrine growth factor for PMCs.

This article has been cited by other articles:

				M. E. Ramos-Nino, L. Scapoli, M. Martinelli, S. Land, and B. T. Mossman Microarray Analysis and RNA Silencing Link fra-1 to cd44 and c-met Expression in Mesothelioma Cancer Res., July 1, 2003; 63(13): 3539 - 3545. [Abstract] [Full Text] [PDF]

				S. N. Georas, L. A. Beck, and C. Stellato What Is Eotaxin Doing in the Pleura? . Insights into Innate Immunity from Pleural Mesothelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 384 - 387. [Full Text] [PDF]

				H. Katayama, A. Yokoyama, N. Kohno, K. Sakai, K. Hiwada, H. Yamada, and K. Hirai Production of Eosinophilic Chemokines by Normal Pleural Mesothelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 398 - 403. [Abstract] [Full Text] [PDF]

				B. T. Mossman and D. C. Gruenert SV40, Growth Factors, and Mesothelioma . Another Piece of the Puzzle Am. J. Respir. Cell Mol. Biol., February 1, 2002; 26(2): 167 - 170. [Full Text] [PDF]

				S. E. Mutsaers, D. Whitaker, and J. M. Papadimitriou Stimulation of Mesothelial Cell Proliferation by Exudate Macrophages Enhances Serosal Wound Healing in a Murine Model Am. J. Pathol., February 1, 2002; 160(2): 681 - 692. [Abstract] [Full Text] [PDF]

				C. MARIE, M.-R. LOSSER, C. FITTING, N. KERMARREC, D. PAYEN, and J.-M. CAVAILLON Cytokines and Soluble Cytokine Receptors in Pleural Effusions from Septic and Nonseptic Patients Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1515 - 1522. [Abstract] [Full Text]