title: Additive effect of Interleukin-12 and Interleukin-18 on the T-helper cell pathway of malignant pleural effusion.
abstract: Interleukin-18 (IL-18) is a novel cytokine with interferon-gamma (IFN-gamma)-inducing activity, thus favoring the T-helper type 1 (Th-1) pathway. The present study attempts to define the role of IL-18 on the functions of lymphocytes isolated from malignant pleural effusions (EAL, effusion-associated lymphocytes). EAL from 10 patients with malignant pleural effusion were incubated with IL-2, IL-12, or IL-18 with/without a alpha CD3 antibody. ELISA, proliferation, and cytotoxicity assays were performed. IL-18 alone was found to have no significant effect on EAL in terms of cytokine production, lymphocyte proliferation, or cytotoxicity against tumor targets. IL-18 also had no significant additive or synergistic effect on IL-2, IL-12, or alpha CD3 co-cultured EAL. However, when IL-18 was used with IL-12, the highest IFN-gamma/IL-10 ratio was derived, suggesting that these two cytokines had an additive effect in leading EAL from the Th-2 to the Th-1 pathway. Furthermore, 1 of 5 patients' EAL had its strongest cytolytic activity against an autologous tumor when the EAL was cultured with IL-2 plus IL-18, as compared with the other 4 patients whose EAL cytolytic activity against autologous tumor was highest when using IL-2 plus alpha CD3. These findings suggest that IL-18 alone did not have a significant effect on EAL, and that IL-18 did not enhance alpha CD3's activity on EAL. However, its additive effect with IL-12 in the Th-1 pathway and with IL-2 in its cytolytic activity against an autologous tumor deserve further studies.
authors.affiliation: Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.
authors.forename: N S
authors.initials: NS
authors.lastname: Yao
authors.forename: Y M
authors.initials: YM
authors.lastname: Chen
authors.forename: R P
authors.initials: RP
authors.lastname: Perng
authors.forename: J
authors.initials: J
authors.lastname: Whang-Peng
mesh_terms: D000230:Adenocarcinoma / Q000150:complications; D000368:Aged; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D008175:Lung Neoplasms / Q000150:complications; D008297:Male; D016066:Pleural Effusion, Malignant / Q000276:immunology / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D020382:Interleukin-18; D018664:Interleukin-12