Pharmaceutical composition containing SAA for use in the treatment of acute and chronic dysregulated inflammatory diseases or conditions

摘要

The present invention describes a novel intervention strategy for the treatment of dysregulated inflammations by using hepatic acute phase proteins serum amyloid A (SAA), CXCL-1/GRO-1/KC or C-reactive protein (CRP) or neutralizing antibodies to these proteins as diseases modulators. The said proteins are to be used as pharmaceutical compositions in the treatment of conditions and diseases characterized by dysregulated inflammations. Besides direct anti-inflammatory as well as host-defensive effects, a hitherto unrecognized regulation of myeloid-derived suppressor cells (MDSC) is uncovered. Myeloid derived suppressor cells seem to be key regulators of inflammatory responses during sepsis and thus represent a valuable target for treatment of these disorders. In a further aspect, the present invention concerns the use of effective amounts of the above identified active agents for activation and mobilisation of MDSC for treatment of excessive dysregulated inflammatory diseases. Further the use of neutralizing antibodies or small molecular inhibitors to treat conditions of suppressed inflammatory responses such as cancer is claimed. The present invention proposes the use of blocking antibodies to SAA, CXCL-1/GRO-1/KC and CRP to prevent MDSC activity and thus boost anti-tumor immune responses in cancer.