ROLE OF 1,25-DIHYDROXYVITAMIN-D3 IN THE GENERATION OF THE ACUTE-PHASERESPONSE IN RATS WITH TALC-INDUCED GRANULOMATOSIS

Subcutaneous injection of nonspecific irritants such as magnesium sili cate (talc) provokes granulomatous inflammation in the rat. Part of th e acute phase response (APR) in these animals is the loss of trabecula r bone at sites distant from the site of inflammation. To assess the p ossible involvement of vitamin D in the bone loss, we studied the deve lopment of the acute phase response in vitamin D-deprived rats. The se rum APR provoked by subcutaneous inflammation in rachitic rats consist ed of hypozincemia, hypercupremia, increased alkaline phosphatase acti vity and adrenocorticotropic hormone (ACTH) concentration, and was sim ilar to that in control animals except for the absence of hypoferremia . Control rats with talc-induced subcutaneous inflammation also had sp lenomegaly and decreased total and mononuclear peripheral blood cell c ounts, while subcutaneous inflammation did not induce spleen changes i n rachitic rats. Subcutaneous inflammation induced the loss of trabecu lar bone and decreased the osteoblastic cell count in tibial metaphyse s in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparabl e to that of the controls. Subcutaneous inflammation did not affect an y of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phas e response during inflammation, particularly in the induction of splee n and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that there m ay be divergent pathways in the generation of the inflammatory respons e, some of which may be dependent on vitamin D.