Interleukin-6 modulates trabecular and endochondral bone turnover in the nude mouse by stimulating osteoclast differentiation

A great deal of evidence has been accumulating that implicates the immune s ystem in normal and pathological bone turnover. The objective of the presen t study was to examine the possible involvement of cytokines produced by T lymphocytes in bone metabolism, We have chosen the immunologically compromi sed athymic mouse, which demonstrate sclerotic features in its trabecular h one, as the animal model for assessment of possible modulation effects of i nterleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6) on bone and cartil age metabolism, The cytokines were applied by daily subcutaneous injections for 3 consecutive days. Histomorphometry, measuring epiphyseal trabecular bone volume (ETBV), metaphyseal trabecular bone volume (MTBV), and the widt h of the growth plate, and tartrate-resistant acid phosphatase (TRAP) histo chemistry were used to assess parameters of bone turnover in the proximal t ibia, IL-6, but not IL-1 alpha, reduced ETBV and MTBV. Both IL-6 and IL-1 a lpha reduced the width of the growth plate. IL-6, but not IL-1 alpha, incre ased the number of chondroclasts and osteoclasts in the primary spongiosa o f the proximal tibia, as well as the number of nuclei. The resultant bone r esembled that of the wild-type mouse, The results point to IL-6 as a possib le regulator of bone turnover In vivo. It is suggested that the athymic mou se has a deficiency somewhere in the cascade of events leading to the produ ction of IL-6 or, alternatively, that IL-6 replaces other factors that are supplied by T lymphocytes directly or indirectly. As T lymphocytes interact with B lymphocytes it is suggested that the athymic mouse might be appropr iate for studying the in vivo effects of the immune system on normal bone m etabolism (C) 2000 by Elsevier Science Inc. All rights reserved.