Interleukin 6 is an autocrine growth factor for normal human pleural mesothelial cells.
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.
Fujino
S
S
Second Department of Internal Medicine, Ehime University, School of Medicine, Japan.
Yokoyama
A
A
Kohno
N
N
Hiwada
K
K
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000502:physiology*; D010994:Pleura / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D019947:Receptors, Interleukin-6
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D006133:Growth Substances; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D003907:Dexamethasone