PMID- 14719133 OWN - NLM STAT- MEDLINE DCOM- 20040308 LR - 20220318 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 13 IP - 2 DP - 2004 Feb TI - Expression of IL-18 in patients with head and neck squamous cell carcinoma. PG - 267-72 AB - Interleukin-18 (IL-18), a recently described cytokine secreted mainly by macrophages, stimulates interferon-gamma (IFN-gamma) production by natural killer cells and T cells. The purpose of this study was to determine tissue expression and serum levels of IL-18 in head and neck squamous cell carcinoma (HNSCC) and to evaluate ethanol and endotoxin-driven cytokine secretion. In 24 patients with primary HNSCC and 28 healthy controls, PBMC were isolated and incubated with 50 mM ethanol, LPS (doses 25 ng/ml, 250 ng/ml, 2500 ng/ml) and both agents for 24 h. Levels of IL-18 in serum, and cell supernatants were analysed by capture ELISA, IL-18 tissue level by immunoblotting. Serum levels of IL-8, IL-10 and IL-12, IFN-gamma, and endotoxin plasma levels were also determined. Statistical analysis involved Welch t-test and Page's test for trend. The majority of patients with HNSCC had high concentrations of serum IL-18. The level of IL-18 in the sera of these patients had a mean level of 271.7 pg/ml, while the mean IL-18 serum level in healthy controls was 174,0 pg/ml (p<0.001). Levels of IL-10 and IL-12, IFN-gamma were not increased in patients. Endotoxin was not detectable in either group. LPS stimulated dose-dependently IL-18 secretion from PBMC of patients and controls in vitro (p<0.05). Incubation with ethanol alone did not affect basal IL-18 secretion, but ethanol reduced LPS-stimulated IL-18 secretion compared to LPS stimulation alone. The mRNA expression of IL-18 in unstimulated PBMC and the response of PBMC to ethanol and LPS was similar in patients and controls. Our data on elevated serum levels of IL-18 in the majority of HNSCC cancer patients, irrespective of its biological activity, suggest that serum IL-18 might be a candidate for a new marker for HNSCC. The pathways for IL-18 production and its mechanisms of action in patients with HNSCC remain to be determined. Understanding of the immunological pathways might offer new therapeutic options in head and neck cancer in the future. FAU - Riedel, Frank AU - Riedel F AD - Universitats-HNO-Klinik, Theodor-Kutzer-Ufer, D-68135 Mannheim, Germany. frank.riedel@hno.ma.uni-heidelberg.de FAU - Adam, Sylvie AU - Adam S FAU - Feick, Peter AU - Feick P FAU - Haas, Stephan AU - Haas S FAU - Gotte, Karl AU - Gotte K FAU - Hormann, Karl AU - Hormann K CN - Mannheim Alcohol Study Group LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Interleukin-18) SB - IM MH - Carcinoma, Squamous Cell/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Head and Neck Neoplasms/*metabolism MH - Humans MH - Interleukin-18/biosynthesis/blood/*genetics MH - Leukocytes, Mononuclear/metabolism MH - Male MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2004/01/14 05:00 MHDA- 2004/03/09 05:00 CRDT- 2004/01/14 05:00 PHST- 2004/01/14 05:00 [pubmed] PHST- 2004/03/09 05:00 [medline] PHST- 2004/01/14 05:00 [entrez] PST - ppublish SO - Int J Mol Med. 2004 Feb;13(2):267-72.