title: Interleukin-7 and interleukin-12 have different effects in rescue of depressed cellular immunity: comparison of malignant and tuberculous pleural effusions.
abstract: The present study attempts to determine the role of interleukin-7 (IL-7) and IL-12 in recovering the functions of the lymphocytes of malignant effusion, in terms of cytokine production, proliferation, and cytolytic activity, compared with lymphocytes from tuberculous pleural effusion. Effusion-associated lymphocytes (EAL) were isolated from tuberculous (tEAL) and malignant (mEAL) pleural effusions. The EAL proliferate response was measured after 3 days in culture. Interferon-gamma (IFN-gamma) production and cytotoxicity against K-562 cells or autologous tumor cells were assessed after 6 days in culture. It was found that the mEAL had depressed proliferation, IFN-gamma production, and cytolytic activity, as compared with tEAL. Stimulation with IL-12 plus IL-2, but not with IL-7 plus IL-2, fully restored the IFN-gamma production of mEAL to that of tEAL levels. In contrast, the proliferate response of mEAL was enhanced significantly more with IL-7 plus IL-2 than with IL-12 plus IL-2. Both the IL-7 plus IL-2 and IL-12 plus IL-2 stimulation of mEAL showed a significant increase in cytolytic activity against autologous tumor cells, although the cytolytic activity against K-562 cells did not increase. These results suggest that tEAL had a higher cellular activity than mEAL. This depressed cellular function of mEAL could be reversed with cytokines. However, different cytokines had different effects on mEAL; for example, IL-7 had a better effect in the stimulation of lymphocyte proliferation compared with IL-12, which had a better effect in driving the lymphocytes to the T helper 1 (TH1) pathway and a higher IFN-gamma production. Both IL-7 and IL-12, in the presence of IL-2, can restore the immunosuppressed cytolytic activity of the lymphocytes of malignant pleural effusion against autologous tumor.
authors.affiliation: Chest Department, Taipei Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan. ymchen@vghtpe.gov.tw
authors.forename: Y M
authors.initials: YM
authors.lastname: Chen
authors.forename: C M
authors.initials: CM
authors.lastname: Tsai
authors.forename: J
authors.initials: J
authors.lastname: Whang-Peng
authors.forename: R P
authors.initials: RP
authors.lastname: Perng
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004357:Drug Synergism; D004654:Empyema, Tuberculous / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D010996:Pleural Effusion / Q000276:immunology*; D016066:Pleural Effusion, Malignant / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D015851:Interleukin-7; D018664:Interleukin-12; D007371:Interferon-gamma