The invention is directed to methods suitable for detecting the presence of a plurality of immune system modulators in a complex solution by running a single sample through a mass spectrometer without any surface preparation or preliminary purification step. Immune system modulators that can be analyzed with the methods of the present invention include cytokines (interferons and interleukins), chemokines, host cell response molecules, and peptide fragments. The method also allows the identification of truncated receptors for immune modulators secreted by infected cells or pathogens, such as virokines, and other pathogen-encoded proteins that affect the host immune system.