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Adami S, Bhalla, AK Dorizzi R, Montesanti F, Rosini S, Salvagno G & Lo CV (1987): The acute-phase response after bisphosphonate administration. Calcif Tissue Int. 41, 326-331.

Adams OR (1987): Lameness in horses. 4th edn. Philadelphia: Lea and Febiger.

Ahn JM, Huang CC & Abramson M (1990): Interleukin 1 causing bone destruction in middle ear cholesteatoma. Otolaryngol. Head Neck Surg. 103, 527-536.

Binderman I, Zor U, Kaye AM, Shimshoni Z, Harell A & Somjen D (1988): The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2. Calcif Tissue Int. 42, 261-266.

Boosalis MG, Gray D, Walker S, Sutliff S, Talwalker R & Mazumder A (1992): The acute phase response in autologous bone marrow transplantation. J. Med. 23, 175-194.

Bowen BL & Fauci AS (1993): Inflammation-Basic principles and clinical correlates. New York: Raven Press.

Canalis E (1987): Effects of tumor necrosis factor on bone formation in vitro. Endocrinology 121, 1596-1604.

Catherwood BD, Onishi T & Deftos LJ (1983): Effect of estrogens and phosphorus depletion on plasma calcitonin in the rat. Calcif: Tissue Int. 35, 502-507.

Centrella M, McCarthy T L & Canalis E (1988): Tumor necrosis factor-alpha inhibits collagen synthesis and alkaline phosphatase activity independently of its effect on deoxyribonucleic acid synthesis in osteoblast-enriched bone cell cultures. Endocrinology 123, 1442-1448.

Cochran DL & Abernathy CK (1988): Modulation of bone resorption by glycosaminoglycans: effects of parathyroid hormone and interleukin-1. Bone 9, 331-335.

Collart MA, Belin D, Vassalli J-D, Kossodo S & Vassalli P (1986): Interferon enhances macrophage transcription of the tumor necrosis factor alpha/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J. Exp. Med. 164, 2113-2118.

Cross AS, Sadoff JC, Kelly N, Bernton E & Gemski P (1989): Pretreatment with recombinant murine tumor necrosis factor alpha/cachectin and murine interleukin I alpha protects mice from lethal bacterial infection. J. Exp. Med. 169, 2021-2027.

Das UN (1991): Interactions between essential fatty acids, eicosanoids, cytokines, growth factors and free radicals: relevance to new therapeutic strategies in rheumatoid arthritis and other collagen vascular diseases. Prostaglandins Leukot. Essent. Fatty Acids 44, 201-210.

Dedhar S (1989): Regulation of expression of the cell adhesion receptors, integrins, by recombinant human interleukin-1 beta in human osteosarcoma cells: inhibition of cell proliferation and stimulation of alkaline phosphatase activity. J. Cell. Physiol. 138, 291-299.

Dower S K, Kronheim SR, March CJ, Conlon PJ, Hopp T P, Gillis S & Urdal DL (1985): Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J. Exp. Med. 162, 501-515.

Enomoto M, Pan HO, Kinoshita A, Yutani Y, Suzuki F & Takigawa M (1990): Effects of tumor necrosis factor alpha on proliferation and expression of differentiated phenotypes in rabbit costar chondrocytes in culture. Calcif: Tissue Int. 47, 145-151.

Evequoz V, Trechsel U & Fleisch H (1985): Effect of bisphosphonates on production of interleukin l-like activity by macrophages and its effect on rabbit chondrocytes. Bone 6, 439-444.

Fujii Y, Sato K, Kasono K, Satoh T, Fujii T & Shizume K (1990): Prolonged and ubiquitous inhibition by interferon gamma of bone resorption induced by parathyroid hormone-related protein, 1,25-dihydroxyvitamin D3, and interleukin 1 in fetal mouse forearm bones. Calcif Tissue Int. 47, 178-182.

Fujita T, Matsui T, Nakao Y, Shiozawa S & Imai Y (1990): Cytokines and osteoporosis. Ann. N.Y Acad. Sci. 587, 371-375.

Garrett IR & Mundy GR (1989): Relationship between interleukin-1 and prostaglandins in resorbing neonatal calvaria. J. Bone Miner. Res. 4, 789-794.

Goldring MB & Goldring SR (1990): Skeletal tissue response to cytokines. Clin. Orthop., 245-278.

Goodship AE & Oryan A (1993). (Unpublished)

Gowen M, MacDonald BR & Russell RG (1988): Actions of recombinant human gamma-interferon and tumor necrosis factor alpha on the proliferation and osteoblastic characteristics of human trabecular bone cells in vitro. Arthritis Rheum. 31, 1500-1507.

Gowen M, Nedwin GE & Mundy GR (1986): Preferential inhibition of cytokine-stimulated bone resorption by recombinant interferon gamma. J. Bone Miner. Res. 1, 469-474.

Grunfeld C & Feingold KR (1992): Tumor necrosis factor, interleukin, and interferon induced changes in lipid metabolism as part of host defense. Proc. Soc. Exp. Biol. Med. 200, 224-227.

Hanazawa S, Ohmori Y, Amano S, Hirose K, Miyoshi T, Kumegawa M & Kitano S (1986): Human purified interleukin-1 inhibits DNA synthesis and cell growth of osteoblastic cell line (MC3T3-E1), but enhances alkaline phosphatase activity in the cells. FEBS Lett. 203, 279-284.

Hashimoto J, Yoshikawa H, Takaoka K, Shimizu N, Masuhara K, Tsuda T, Miyamoto S & Ono K (1989): Inhibitory effects of tumor necrosis factor alpha on fracture healing in rats. Bone 10, 453-457.

Hirokawa M, Takatsu H, Niitsu H, Nishinari T, Nimura T, Itoh T, Chubachi A, Miura I, Yoshida K, Endo Y & Miura AB (1989): Serum tumor necrosis factor-alpha levels in allogeneic bone marrow transplant recipients with acute leukemia. Tohoku J. Exp. Med. 159, 237-244.

Hopkins SJ (1990): Cytokines and eicosanoids in rheumatic disease. Ann. Rheum. Dis. 49, 207-211.

Hurley MM, Fall P, Harrison JR, Petersen DN Kream BE & Raisz LG (1989): Effects of transforming growth factor alpha and interleukin-1 on DNA synthesis, collagen synthesis, procollagen mRNA levels, and prostaglandin E2 production in cultured fetal rat calvaria. J. Bone Miner. Res. 4, 731-736.

Ikeda E, Kusaka M, Hakeda Y, Yokota K, Kumegawa M & Yamamoto S (1988): Effect of interleukin I beta on osteoblastic clone MC3T3-E1 cells. Calcif. Tissue Int. 43, 162-166.

Isaacs A & Lindenmann J (1957): Virus interference I: the interferon. Proc. R. Soc. Lond. 147, 258-250.

Jacobs TW, Joffe II, Katz IA, Stein B, Li MK, Ke HZ, Jee WS & Epstein S (1992): Interferon gamma fails to prevent cyclosporine A induced osteopenia in the rat. Bone Miner. 17S, 202.

Jennings G, Bourgeois C & Elia M (1992): The magnitude of the acute phase protein response is attenuated by protein deficiency in rats. J. Nutr. 122, 1325-1331.

Klaushofer K, Horandner H, Hoffmann O, Czerwenka E, Konig U, Koller K & Peterlik M (1989): Interferon gamma and calcitonin induce differential changes in cellular kinetics and morphology of osteoclasts in cultured neonatal mouse calvaria. J. Bone Miner. Res. 4, 585-606.

Konig A, Muhlbauer RC & Fleisch H (1988): Tumor necrosis factor alpha and interleukin-1 stimulate bone resorption in vivo as measured by urinary [3H]tetracycline excretion from prelabeled mice. J. Bone Miner. Res. 3, 621-627.

Lewis GP (1986): Mediators of inflammation. Bristol: Wright.

Louw JA, Werbeck A, Louw MEJ, Kotze TJVW, Cooper R & Labadarios D (1992): Blood vitamin concentrations during the acute-phase response. Crit. Care Med. 20, 934-941.

Mazlam MZ & Hodgson HJF (1992): Peripheral blood monocyte cytokine production and acute phase response in inflammatory bowel disease. Gut 33, 773-778.

McGlave P (1990): Bone marrow transplants in chronic myelogenous leukemia: an overview of determinants of survival. Sem. Hematol. 27, 23-30.

Nanes MS, McKoy WM & Marx SJ (1989): Inhibitory effects of tumor necrosis factor-alpha and interferon-gamma on deoxyribonucleic acid and collagen synthesis by rat osteosarcoma cells (ROS 17/2. 8). Endocrinology 124, 339-345.

Nanes MS, Rubin J, Titus L, Hendy GN & Catherwood BD (1990): Interferon-gamma inhibits 1,25-dihydroxyvitamin D3-stimulated synthesis of bone GLA protein in rat osteosarcoma cells by a pretranslational mechanism. Endocrinology 127, 588-594.

Nathan CF & Sporn MB (1991): Cytokines in context. J. Cell. Biol. 113, 981-986.

Nawroth PP, Bank I, Handley D, Cassimeris J, Chess L & Stern D (1986): Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J. Exp. Med. 163, 1363-1375.

O'Keefe RJ, Crabb ID, Puzas JE & Rosier RN (1992): Influence of prostaglandins on DNA and matrix synthesis in growth plate chondrocytes. J. Bone Miner. Res. 7, 397-404.

Ohmori Y, Hanazawa S, Amano S, Hirose K, Kumegawa M & Kitano S (1988): Effects of recombinant human interleukin 1 alpha and interleukin 1 beta on cell growth and alkaline phosphatase of the mouse osteoblastic cell line MC3T3-E1. Biochim. Biophys. Acta 970, 22-30.

Rath NC, Oronsky, AL & Kerwar SS (1988): Synthesis of interleukin-1-like activity by normal rat chondrocytes in culture. Clin. Immunol. Immunopathol. 47, 39-46.

Saito S, Ngan P, Saito M, Lanese R, Shanfeld J & Davidovitch Z (1990): Interactive effects between cytokines on PGE production by human periodontal ligament fibroblasts in vitro. J. Dent. Res. 69, 1456-1462.

Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong GHW, Gatanaga T, Granger GA, Lentz R, Raab H, Kohr WJ & Goeddel DV (1990): Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 61, 361-370.

Seckinger P, Kleinnulend J, Alander C, Thompson RC, Dayer JM & Raisz LG (1990): Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production. J. Immunol. 145, 4181-4184.

Shapiro S, Tatakis DN & Dziak R (1990): Effects of tumor necrosis factor alpha on parathyroid hormone-induced increases in osteoblastic cell cyclic AMP. Calcif Tissue Int. 46, 60-62.

Shen V, Kohler G, Jeffrey JJ & Peck WA (1988): Bone-resorbing agents promote and interferon-gamma inhibits bone cell collagenase production. J. Bone Miner. Res. 3, 657-666.

Shen V, Cheng SL, Kohler NG & Peck WA (1990): Characterization and hormonal modulation of IL-1 binding in neonatal mouse osteoblastlike cells. J. Bone Miner Res. 5, 507-515.

Shinohara O, Kato S, Yabe H, Yabe M, Kubota C, Mitsuda R & Kimura M (1991): Growth after bone marrow transplantation in children. Am. J. Pediatr. Hematol. Oncol. 13, 263-268.

Skerry TM, Bitensky L, Chayen J & Lanyon LE (1989): Early strain-related changes in enzyme activity in osteocytes following bone loading in vivo. J. Bone Miner. Res. 4, 783-788.

Skerry TM, Suswillo R, el HA, Ali NN, Dodds RA & Lanyon LE (1990): Load-induced proteoglycan orientation in bone tissue in vivo and in vitro. Calcif Tissue Int. 46, 318-326.

Smith CA, Davis T, Anderson DC, Solam L, Beckmann MP, Jerzy R, Dower SK, Cosman D & Goodwin RG (1990): A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 248, 1019-1025.

Stashenko P, Dewhirst FE, Peros WJ, Kent RL & Ago JM (1987): Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. J. Immunol. 138, 1464-1468.

Streuli CH, Schmidhauser C, Kobrin M, Bissell MJ & Derynck R (1993): Extracellular matrix regulates expression of the TGF-beta 1 gene. J. Cell. Biol. 120, 253-260.

Strunk RC, Cole FS, Perlmutter DH & Colten HR (1986): Gamma interferon increases expression of complement genes in human macrophages. J. Biol. Chem. 260, 15280-15285.

Suva LJ, Seedor JG, Endo N, Quartuccio HA, Thompson DD, Bab I & Rodan GA (1993): The differential pattern of gene expression during bone formation following rat tibial marrow ablation. J. Bone Miner. Res. 83, 379-388.

Takahashi N, Mundy GR & Roodman GD (1986): Recombinant human interferon-gamma inhibits formation of human osteoclast-like cells. J. Exp. Med. Immunol. 137, 3544-3549.

Trinchieri G, Matsumoto-Kobayashi M, Clark SV, London L & Perussia B (1984): Response of human peripheral blood natural killer cells to interleukin-2. J. Exp. Med 160, 1147-1140.

Vignery A, Niven FT & Shepard MH (1990): Recombinant murine interferon-gamma inhibits the fusion of mouse alveolar macrophages in vitro but stimulates the formation of osteoclastlike cells on implanted synergenic bone particles in mice in vivo. J. Bone Miner. Res. 5, 637-644.

Wegenka UM, Buschmann J, Lutticken C, Heinrich PC & Horn F (1993): Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level. Mol. Cell. Biol. 13, 276-288.

Weinberg JB & Larrick JW (1987): Receptor-mediated monocytoid differentiation of human promyelocytic cells by tumor necrosis factor: synergistic actions with interferon-gamma and 1,25-dihydroxyvitamin D3 (published erratum appears in Blood 71(1), 272, Jan. 1988). Blood 70, 994-1002.

Yoshihara R, Shiozawa S, Imai Y & Fujita T (1990): Tumor necrosis factor alpha and interferon gamma inhibit proliferation and alkaline phosphatase activity of human osteoblastic SaOS-2 cell line. Lymphokine Res. 9, 59-66.

Yoshikawa H, Hashimoto J, Masuhara K, Takaoka K & Ono K (1988): Inhibition by tumor necrosis factor of induction of ectopic bone formation by osteosarcoma-derived bone-inducing substance. Bone 9, 391-396.


Until now, experimental work on growth plates has mainly concentrated on the characterization of processes going on in a normal growth plate, rather than on systematic changes of conditioning factors; one therefore has not yet identified the dominant processes in relation with the growth plate that are either enhanced or reduced by inflammatory processes.

Various proteins and protein inhibitors play an important role in the inflammatory response, which is therefore modified in children suffering from protein-energy malnutrition. It can be hypothesized that, to mount an adequate inflammatory response, not only quantitative requirements for protein but also for specific amino acids have to be met. Looking for instance at the amino acid composition of acute phase proteins, one can speculate what the requirements for these might be for an acute phase response, but the experimental work to test this hypothesis has not yet been done.

Different cells involved in bone formation and growth have different metabolisms and nutritional substrate requirements. Osteoclasts for instance are quite different from other bone cells insofar as they use a fatty acid oxidative process to meet their energy requirements.

Essential fatty acids of the omega-6 and omega-3 type affect growth in animal studies. Traditionally, only omega-6 fatty acids have been considered necessary for humans, but recent evidence suggests that omega-3 fatty acids are also essential for normal brain growth and development. Low levels of arachidonic acid in formula fed preterm infants were associated with decreased weight and length gain in the first year of life.

The same seems to be true for cells involved in the inflammatory response. Monocytes, that produce and secrete cytokines, are activated by essential fatty acids. In osteoporotic women who were treated by hormone replacement therapy, changes in cytokine secretion from monocytes were observed.

The inflammatory response can exert an effect on growth via hormones acting not only locally, but also systemically. Cortisol, for instance, has a catabolic effect on the growth plate, and hepatic IGF-I production drops dramatically as part of the acute phase response. Unfortunately there is as yet little information on the range and intensity of these responses to different types and severities of infection. The experimental work done so far has usually been on a few clearly defined and fairly strong challenges to the system. We need to know more on effects of common types of low-level infections and on whether they still produce an inflammatory response that is sufficient to affect bone growth. Scientists working on cytokines have been focusing their attention primarily on effects on immune responses and not on growth.

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