Production of bioactive and immunoreactive interleukin-6 (IL-6) and expression of IL-6 messenger ribonucleic acid by human pituitary adenomas.
Preliminary studies have demonstrated that some pituitary adenomas secrete immunoreactive interleukin-6 (irIL-6) when cultured in vitro. We have extended these studies by investigating 100 pituitary adenomas of different types measuring immunoreactive and bioactive IL-6. Tumors were cultured either as explants without fetal calf serum or as dispersed cells with 10% total calf serum. Fifty-three of the 100 (53%) pituitary cultures were found to release irIL-6 and in 44 adenomas examined, 32 (72.7%) secreted bioactive IL-6. In 61 explant cultures, 30 adenomas released IL-6, indicating autonomous secretion. The amount of IL-6 released by adenomas in cell culture was generally higher, although the incidence was similar to explant cultures. IrIL-6 was released by 7 of 14 prolactinomas, 15 of 27 somatotrophinomas, 5 of 7 corticotrophinomas (including 2 Nelson's adenomas), 1 of 1 thyrotrophinomas, 2 of 2 gonadotrophinomas, and 23 of 49 clinically non-functioning adenomas. Periadenomatous tissue removed from a patient with a corticotrophinoma was found to secrete IL-6 but in much lower concentration than from the adenoma tissue. Tumor necrosis factor-alpha and -gamma-interferon were not detected in the conditioned media. Four IL-6-secreting adenomas were examined by in situ hybridization for IL-6 messenger RNA, and three of these were positive with fluorescence present throughout the tissue examined. We have provided evidence that over half of pituitary adenomas secrete IL-6 which is bioactive and that IL-6 is synthesized within the tumor by the adenoma cells.
Jones
T H
TH
University Department of Medicine, Northern General Hospital, Sheffield, England.
Daniels
M
M
James
R A
RA
Justice
S K
SK
McCorkle
R
R
Price
A
A
Kendall-Taylor
P
P
Weetman
A P
AP
D000236:Adenoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003470:Culture Media / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
D003470:Culture Media; D015850:Interleukin-6; D012333:RNA, Messenger