Clinical Adverse Effects of Cytokines on the Immune System

Many clinical studies or case reports have focused on the clinical consequences of immunoenhancement or immune dysregulation mediated by therapeutic cytokines. Flu-like reactions, and the facilitation or exacerbation of inflammatory diseases, are the main consequences of immunoenhancement. Flu-like symptoms commonly are observed in patients treated with interferons, interleukin (IL)-1, IL-2, IL-3, or tumor necrosis factor-α. They typically consist of fever and chills, malaise, tachycardia, arthralgias, and myalgias that develop within a few hours after administration. The mechanism is not clearly understood but probably involves the acute release of fever-promoting factors in the hypothalamus. Because various cytokines are directly or indirectly involved in the pathogenesis of immune-mediated inflammatory disorders and autoimmune diseases, it is not surprising that such disorders develop after the administration of pharmacological doses of these cytokines. Another adverse consequence is the development of cytokine-specific antibodies in the sera of treated patients.