The human Clara cell protein: biochemical and biological characterisation of a natural immunosuppressor.

The Clara cell protein, the human counterpart of rabbit uteroglobin, exerts an anti-inflammatory action by interfering in different ways with the cytokine-network. Firstly, CC16 behaves like an anti-cytokine by downregulating the production of IFN-gamma, IL-1 and TNF-alpha by stimulated leukocytes. The extent of inhibition depends on the inducing agent (being maximal when IL-2 is used as inducer) and varies with the applied concentration of CC16. Secondly, the protein reduces the antiviral activity and the augmentation of phagocytosis induced by IFN-gamma. In both cases (inhibition of production and biologic activity) there is a 50% reduction in the presence of 10 ng/ml CC16. The natural and IFN-gamma-enduced cytotoxicity of NK-cells however, are enhanced by the presence of CC16, indicating a more complex interaction of CC16 with the immune-system. The immunosuppressive properties make CC16 a promising agent for the treatment of inflammatory reactions and auto-immune diseases.