Methods of using Metrnl/IL-41 to identify inflammation, inflammatory and autoimmune diseases, infection and cancer in a subject are provided. The methods include determining the serum or plasma levels of Metrnl/IL-41 in the subject. Methods of modulating a condition selected from cytokine release syndrome, systemic immune response syndrome, cytokine storm, or a combination thereof, using Metrnl/IL-41 or antibodies against Metrnl/I-41 are also provided.