Methods of treatment using IL-27 antagonists are provided. Such methods include, but are not limited to, methods of treating steroid-resistant conditions, such as asthma, chronic obstructive pulmonary disease (COPD), systemic lupus erythematosus (SLE), and inflammatory bowel disease. Such antagonists include, but are not limited to, antibodies that bind IL-27 and inhibit IL-27-mediated signaling (such as, for example, by blocking binding of IL-27 to its receptor) antibodies that bind the IL-27 receptor, alpha subunit, and inhibit IL-27-mediateed signaling (such as, for example, by blocking binding of IL-27 to the receptor) and soluble forms of IL-27RA.