Complex patterns of regulation of chemokine secretion by Th2-cytokines, dexamethasone, and PGE2 in tuberculous osteomyelitis.

Tuberculous osteomyelitis is characterized by uncontrolled inflammation leading to bone destruction. Chemokines recruit inflammatory cells but there are no data on the mechanisms limiting cell influx. We investigated the potential down-regulators of chemokine secretion IL-4, IL-10, IL-13, dexamethasone, and PGE2, IL-10 and IL-13 down-regulate M. tuberculosis-induced IL-8, IP-10, RANTES, and MCP-1 secretion from MG-63 cells by between 48 and 94% (P < 0.05) but do not inhibit chemokine gene transcription. In contrast, IL-4 augments gene expression and secretion of IP-10 from 12,030 +/- 1070 to 24,330 +/- 1720 pg/ml/4 x 10(5) cells (P < 0.01) and RANTES secretion, from 3550 +/- 150 to 6930 +/- 400 pg/ml/4 x 10(5) cells (P < 0.01). Dexamethasone and PGE2 caused a 13-fold down-regulation of secretion of all four chemokines but only dexamethasone inhibits mRNA accumulation. Data from primary osteoblasts were similar. In summary, down-regulation of osteoblastic chemokine secretion was not uniformly observed and the control of chemokine secretion in response to M. tuberculosis is a complex process mediated by pre- and posttranscriptional mechanisms.