The present invention relates generally to a method of modulating cytokine-mediated cellular activity and to agents useful for same. More particularly, the present invention contemplates a method of modulating tumor necrosis factor-mediated cellular activity by modulating an intracellular sphingosine kinase-dependent signalling mechanism. The method of the present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate cytokine-mediated cellular activity The present invention is further directed to methods for identifying and/or designing agents capable of modulating the subject sphingosine kinase-dependent signalling mechanism.