Aggregation of biotherapeutic products continues to be a significant concern for a biopharmaceutical manufacturer due to the likely impact it can have on product safety. Characterization of protein aggregates, as caused by different stresses, is an essential step towards gaining a deeper understanding of a biotherapeutic product. These stresses may be experienced during manufacturing, formulation, filling, storage and/ or shipping. While there is widespread consensus that protein aggregation can enhance immunogenicity, the underlying immunological and biological mechanisms are not completely understood. All manufacturers rely on controls of particulation so as to ensure the safety and efficacy of protein drug products. Cytokines are an important class of biological molecules that regulate distinct functions of different immunocompetent cells. These are key modulators of inflammation, participating in acute and chronic inflammation via a complex network of interactions. Proinflammatory cytokines are important biomarkers and potent mediators of several biological processes. Chronic uncontrolled levels of such cytokines can initiate and formulate many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. This study presents results from an investigation into how aggregates generated by a variety of mechanical and chemical stresses impact pro- and anti- inflammatory cytokine responses. The results affirm that highly aggregated mAb therapeutics can induce the production of pro-inflammatory cytokine responses.