Preliminary report on immunomodulation of mesenchymal stem cells in M.tb infection

Abstract

Tumor necrosis factor-alpha and interferon-gamma are two important pleiotropic inflammatory cytokines that perpetuate tissue damage after increased stress and in the presence of excess glucocorticoids with respect to tuberculosis (TB) infection. Activated macrophage dysfunction leads to granuloma formation, cavities, and fibrosis. Current treatment strategies are not amenable to long-term compliance, contraindications, increased relapse rates, and compounding drug resistance. A natural supplement devoid of the abovementioned complications needs to be developed and checked for healthy immune reconstitution targeting dendritic cell therapy . The preliminary prospective study in five TB subjects was assessed objectively using ELISA for TNF-alpha and interferongamma levels. The PBMCs were mixed and cultured for the effect of allogenic bone marrow-derived mesenchymal stem cell interactions and secretory cytokines in the culture supernatant. The TNF-alpha levels on day five with an MSC dose of 10 cells/ml for 1x10 cells/ml of PBMCs of diseased patients were significantly decreased while there was no change in IFN-gamma levels. The variable dose of MSC appears to have had a significant impact on the cytokine milieu in vitro. The results are encouraging in that there is possibility for effective immune modulation using mesenchymal stem cells in infection-mediated inflammation.