Cytokine production and surface antigen expression by peripheral blood mononuclear cells in postmenopausal osteoporosis

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Abstract
It was reported earlier that IL-1 production by cultured monocytes and the ratio of helper (CD4) to suppressor (CD8) lymphocytes in peripheral blood are different in osteoporotic compared to nonosteoporotic subjects. We examined these and several other parameters related to the biosynthetic activity and differentiation status of peripheral blood mononuclear cells (PBMC) in untreated osteoporotic postmenopausal women (age 65 ± 7, n = 46), nonosteoporotic postmenopausal women (age 55 ± 3, n = 20), and nonosteoporotic premenopausal women (age 37 ± 7, n = 8), as defined by spine density. We found that unstimulated monocytes from osteoporotics did not produce detectable IL-1β as determined by ELISA. In addition, there were no significant differences between osteoporotics and nonosteoporotics in IL-1β or IFN-γ production by PBMC stimulated with OKT3, a monoclonal antibody to the T cell-receptor complex. The proliferative response of lymphocytes to OKT3 was significantly less (p < 0.02) in osteoporotics compared to nonosteoporotic post- and premenopausal women; multiple-regression analysis, however, indicated that this difference was not due to bone density but to age. Flow cytometric analysis of PBMC revealed no difference between osteoporotics and nonosteoporotics in the distribution of 18 phenotypic subsets determined, including CD4-or CD8-positive lymphocytes or the ratio of CD4 to CD8 cells. Further, there was no correlation of the surface markers with bone density, the exceptions being the subsets expressing the CD3/CD56 and CD8/CD56 markers, which were inversely related to spine density in the osteoporotic women. Nonetheless, in the osteoporotic women, the CD8/CD56 and CD14/CD13 cells were positively correlated with the levels of plasma 1,25-(OH)2D3 (r = 0.33, p < 0.04; r = 0.39, p = 0.028, respectively), whereas the CD4 cells were negatively correlated with 1,25-(OH)2D3 (r = −0.35, p = 0.026). These data suggest that cytokine production by peripheral blood mononuclear cells and the distribution of the various subsets of these cells in the peripheral blood are not related to bone mass in osteoporosis. Distribution of PBMC subsets in the peripheral blood, however, may be influenced by circulating levels of 1,25-(OH)2D3.
Funding Information
  • NIH (AI 21761, AR 41313, RR 00750)
  • Veterans Administration
  • Sandoz Research Institute