tumor necrosis factor, and lymphotoxin in. Synergistic interactions between interleukin 1,. P Stashenko, F E Dewhirst, W J Peros, R L Kent and J M Ago.
0022-1767/87/1385-1464$02.00/0
Voi. 138. 1464-1468, No. 5.March 1. 1987
THEJOURNAL OF IMMUNOLCXY Copyright 0 1987 by The American Association of lmmunoioglsts
Prlnted Ln U.S.A.
SYNERGISTIC INTERACTIONS BETWEEN INTERLEUKIN 1, TUMOR NECROSIS FACTOR, AND LYMPHOTOXININ BONE RESORPTION' PHILIP STASHENKO,'+ FLOYD E. DEWHIRST,' WILLIAM J. PEROS,' JOANNE M. AGO'
RALPH L. KENT,
AND
F r o m t h e D e p a r t m e n tof s 'Immunology and 'Pharmacology, Forsyth Dental Center, Boston, MA
Cytokines with bone-resorbingactivity includeIL These include monocyte-derived tumor necrosis factor l a (PI 5), tumor necrosis factor (TNF), (TNF) and the structurally related lymphocyte product and lymphotoxin(LT). Possible interaction between lymphotoxin (LT) (3).both of which are, however, 1000IL 18, the major mediator with osteoclast-activating fold less potent than IL l p (4). Interleukin l a (IL la), factor (OAF) activity, and other cytokines was stud-which is produced by activated macrophages in one-tenth ied. By itself, IL 18 was 13-fold more potent thanIL the amount of IL lp, exhibits parallel activities to IL lp l a and 1000-fold more potent than either TNF or LT in numerous assays (5),including bone resorption (6). in stimulating bone resorption. Suboptimal concenAlthough TNF and LT could be responsible for only a trations of IL 18 or IL l a in combination with sub- small fraction (
