The Role of Th17/IL-17 on Eosinophilic Inflammation

Eosinophilia develops in reactive environment such as allergy, parasitic infections and in hypereosinophilic syndrome [HES]. Activated eosinophils are accompanied by a wide variety of inflammatory response due to release of toxic inflammatory mediators, which may result in severe tissue/organ damage at the site of eosinophilic infiltrations, due to degranulation. The factor responsible for the detrimental effect of activated circulatory eosinophils is an area less explored. In the present study, we determined the serum cytokine milieu of eosinophilic and control subjects, and also investigated the change in the pattern of cytokine released under mitogen stimulation. Increased level of various pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, IL-5 and IL-17 was detected in serum and culture supernatants of endotoxin stimulated white blood cells [WBCs] of eosinophilic subjects compared to control population. It was observed that endotoxin exposure in WBCs of eosinophilic subjects, led to increased release of IL-17, produced by TH17 subset of T-cell, contributing towards eosinophilic exuberations, in vitro. We observed non-specific lysis by eosinophils under such inflammatory milieu and synergistic eosinophilic activity in presence of IL-17 and IL-5 in combination. Taken together, our findings provide vital insight on TH17 lymphocyte mediated activation of eosinophils, via differential cytokine regulation, which play an important role in hypereosinophilic systemic inflammation.

► Eosinophilic cytokine profile is dominated by TH2 and proinflammatory cytokines. ► Endotoxin stimulation in eosinophilic WBCs results in increase of TH17 subset and IL-17 cytokine. ► Increased level of IL-17 enhances eosinophilic cytolysis. ► Eosinophils activation leads to non-specific lysis of target cells. ► Increased IL-17 and IL-5 enhance eosinophil mediated cytolytic activity.