Mechanisms of paraneoplastic syndromes of colon-26: involvement of interleukin 6 in hypercalcemia.
The precise mechanisms responsible for increased calcium levels in patients with cancer are not fully understood. In a recent study, the participation of interleukin (IL)-6 as an important mediator of key parameters of cancer cachexia in the colon-26 adenocarcinoma was reported. Here, we show that in addition to cachexia, C-26 tumour bearing mice also develop hypercalcemia. Treatment of these mice with 5' deoxyfluorouridine significantly reduces tumour size and inhibits both hypercalcemia, cachexia, and elevated serum IL-6. Moreover, monoclonal antibody to mouse IL-6 prevents both the cachexia and the hypercalcemia and reduces serum IL-6 levels in C-26 tumour bearing hosts. The administration of a bisphosphonate compound (Clodronate) reverses the hypercalcemia but has no effect on tumour burden, serum IL-6 levels, or wasting. We conclude that tumour-derived IL-6 plays a role in the pathogenesis of the C-26 associated hypercalcemia, and that the increase of serum calcium does not by itself mediate cachexia.
Strassmann
G
G
Department of Immunology, Otsuka American Pharmaceutical Inc., Rockville, MD 20850.
Jacob
C O
CO
Fong
M
M
Bertolini
D R
DR
D000230:Adenocarcinoma / Q000097:blood* / Q000150:complications; D000818:Animals; D003110:Colonic Neoplasms / Q000097:blood* / Q000150:complications; D006934:Hypercalcemia / Q000209:etiology*; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D010257:Paraneoplastic Syndromes / Q000097:blood*; D011897:Random Allocation
D015850:Interleukin-6